SUJEET KUMAR

I have been working with KLE College of Pharmacy Bangalore (India) since July 2007 in the Department of Pharmaceutical Chemistry (Associate Professor at present). During my master’s (Pharmaceutical Chemistry) and PhD, I worked on nitrogen, oxygen, and sulfur-containing biologically active small heterocyclic molecules. My Post-doctoral research in the Department of Biomaterials Science at the Pusan National University Republic of Korea gave me in-depth knowledge about the functionalization of biopolymers as a drug delivery tool. Multistep synthesis of heterocyclic molecules, their purification and, structural characterization is the area of my research. I believe in teamwork and collaborative research. In the 15 years of teaching & research, I contributed to 35 research articles. Pharmaceutics, Cell, FEBS, Scientific Reports, EJMC, BMCL, Molecular Carcinogenesis and RSC Advances are few among them

EDUCATION

PhD in Pharmaceutical Sciences (JNTU, Hyderabad)

RESEARCH, TEACHING, or OTHER INTERESTS

Drug Discovery, Pharmaceutical Science, Cancer Research, Organic Chemistry

Scopus Publications

Synthesis, molecular docking, dynamics study and preliminary cytotoxicity study of some coumarin linked imidazothiadiazoles
Sujeet Kumar, Sravani PV, Gokulakrishnan S, Satyaprakash Khushwah, Basavaraj Metikurki, Dominique Schols, Hakan Alici, Hakan Tahtaci, Satvik Kotha, Swapna B,et al.
Elsevier BV



Synthesis, in silico ADME, Molecular Docking and in vitro Cytotoxicity Evaluation of Indolin-2-one linked Stilbene Derivatives
Dimple Pirgal, Subhas S. Karki, Sujeet Kumar, and Basavraj Metikurki
Asian Journal of Chemistry
Considering the potential of stilbene derivatives as biologically active frameworks in cancer research, the synthesis of several indole-2-one linked stilbenes was proposed as evaluate their cytotoxic effects on cancer cells. To develop some indole-2-one linked stilbene analogs as lead molecule against cancer, novel indole-2-one linked derivatives (BK 1-11) were synthesized by reacting 4-formyl-trans-stilbene with 2-oxindole in methanol. The structural characterizations were performed by FTIR, NMR and mass techniques. Molecular docking was performed on the Janus kinase 2 (JAK2) receptor (Pdb ID: 4Z32), with binding energies expressed in kcal/mol. All the synthesized compounds were screened for their cytotoxicity against MCF, HCT116 and HeLa cells taking 5-fluorouracil (5-FU) and resveratrol as reference. Among tested derivatives, compound BK-6 was found to be most potent against all the three cell lines with IC50 of 48-64 µM and 49.92% cell viability after 72 h of treatment. A low to moderate aqueous solubility was predicted by Swiss-ADME web-tool. The docking score and cytotoxicity data suggest compound BK-6 as a potential molecule against MCF cancer cells. However, further biological studies require to support the cytotoxicity and in silico results.


Discovery of new pyrazole-4-carboxamide analogues as potential anticancer agents targeting dual aurora kinase A and B
Digambar Yevale, Nishith Teraiya, Twinkle Lalwani, Mayur Dalasaniya, Saumya K. Patel, Nandan Dixit, Chetan B. Sangani, Sujeet Kumar, N.V.L. Sirisha Mulukuri, Tao Huang,et al.
Elsevier BV



Statistical modeling, optimization and characterization of andrographolide loaded emulgel for its therapeutic application on skin cancer through enhancing its skin permeability
N. V. L. Sirisha Mulukuri, Sujeet Kumar, Moumita Dhara, Gupta Dheeraj Rajesh, and Pankaj Kumar
Elsevier BV



Synthesis, In silico Study and Cytotoxicity Evaluation of Some Newly Synthesized Stilbene Derivatives
Dimple Pirgal, Subhas S. Karki, Sujeet Kumar, and Basavraj Metikurki
Asian Journal of Chemistry
A series of 12 stilbene derivatives (23-34) were synthesized by reacting benzyl-triphenylphosphonium chlorides (9-14) and hydrochloride salt of 3,5-disubstituted-4-hydroxybenzaldehydes (21-22). The synthesized molecules were tested against the human breast cancer cell line MCF7 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in 10% Dulbecco’s modified Eagle Medium (DMEM). Compound 23 exhibited significant cytotoxicity, with 1.11% viability at a concentration of 200 µM, compared to the reference standard resveratrol (15.14%) and 5-fluorouracil (51.86%). All the synthesized derivatives demonstrated equipotency to 5-fluorouracil (5-FU) at all the tested concentrations. The docking study was conducted on the tyrosine-protein kinase/Janus Kinase 2(JAK2) receptor using Autodock Vina. The results of the docking study suggest that, with the exception of compounds 29 (-6.7 kcal/mol) and 32 (-7.1 kcal/mol), most of the synthesized derivatives have exhibited glide scores greater than the standard resveratrol (-7.8 kcal/mol). This implies that these compounds 23-34 have a strong binding affinity to the JAK2 receptor, which is relevant in the context of cancer research, as JAK2 is associated with various signaling pathways involved in cell proliferation and survival.


Enhancing the Thermoelectric Power Factor by Lowering the Electrical Resistivity of Bi<inf>2</inf>Se<inf>3</inf>/NaI Composites Prepared by Solid-State Reaction
Vivekananda, P. K. Prarthana, M. Archana, R Gowrishree, Tejashree Bhat, V Prakruthi, N. S. Keerthana, P. Sharath, T. Tabassum Sulthana, R. Thulasi,et al.
Springer Science and Business Media LLC



Synthesis of Novel Pyrazole-Oxindole Conjugates with Cytotoxicity in Human Cancer Cells via Apoptosis
Pravesh M. Jain, Denisse A. Gutierrez, Sujeet Kumar, Renato J. Aguilera, and Subhas S. Karki
Wiley
AbstractA novel series of pyrazole‐oxindole conjugates were prepared and characterized as potential cytotoxic agents by FT‐IR, NMR and HR‐MS. The cytotoxic activity of these compounds was tested in the Jurkat acute T cell leukemia, CEM acute lymphoblastic leukemia, MCF10 A mammary epithelial and MDA‐MB 231 triple negative breast cancer cell lines. Among the tested conjugates, 5‐methyl‐3‐((3‐(1‐phenyl)‐3‐(p‐tolyl)‐1H‐pyrazol‐4‐yl)methylene)indolin‐2‐one 6h emerged as the most cytotoxic with a CC50 of 4.36+/−0.2 μM against Jurkat cells. The mechanism of cell death induced by 6h was investigated through the Annexin V‐FITC assay via flow cytometry. Reactive oxygen species (ROS) accumulation, mitochondrial health and the cell cycle progression were also evaluated in cells exposed to 6h. Results demonstrated that 6h induces apoptosis in a dose‐response manner, without generating ROS and/or altering mitochondrial health. In addition, 6h disrupted the cell cycle distribution causing an increase in DNA fragmentation (Sub G0‐G1), and an arrest in the G0‐G1 phase. Taken together, the 6h compound revealed a strong potential as an antineoplastic agent evidenced by its cytotoxicity in leukemia cells, the activation of apoptosis and restriction of the cell cycle progression.


A Coumarin–Imidazothiadiazole Derivative, SP11 Abrogates Tumor Growth by Targeting HSP90 and Its Client Proteins
Snehal Nirgude, Shahana M. V., Febina Ravindran, Sujeet Kumar, Shivangi Sharma, Raghunandan Mahadeva, Anisha Mhatre, Subhas S. Karki, and Bibha Choudhary
MDPI AG
Despite several treatment options for blood cancer, mortality remains high due to relapse and the disease’s aggressive nature. Elevated levels of HSP90, a molecular chaperone essential for protein folding, are associated with poor prognosis in leukemia and lymphoma. HSP90 as a target for chemotherapy has been met with limited success due to toxicity and induction of heat shock. This study tested the activity of an HSP90 inhibitor, SP11, against leukemic cells, mouse lymphoma allograft, and xenograft models. SP11 induced cytotoxicity in vitro in leukemic cell lines and induced cell death via apoptosis, with minimal effect on normal cells. SP11 induced cell death by altering the status of HSP90 client proteins both in vitro and in vivo. SP11 reduced the tumor burden in allograft and xenograft mouse models without apparent toxicity. The half-life of SP11 in the plasma was approximately 2 h. SP11 binding was observed at both the N-terminal and C-terminal domains of HSP90. C-terminal binding was more potent than N-terminal binding of HSP90 in silico and in vitro using isothermal calorimetry. SP11 bioavailability and minimal toxicity in vivo make it a potential candidate to be developed as a novel anticancer agent.


Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1,2,3-triazole derivatives
Arnika Das, Giulia Greco, Sujeet Kumar, Elena Catanzaro, R. Morigi, A. Locatelli, D. Schols, Hakan Alici, Hakan Tahtaci, Febina Ravindran,et al.




Synthesis, characterization, and biological evaluation of some 4-((thiophen-2-yl-methylene)amino)benzenesulfonamide metal complexes
E. Vijaya Sekhar, Subhas S. Karki, Javarappa Rangaswamy, Mahesh Bhat, and Sujeet Kumar
Springer Science and Business Media LLC
Abstract Background Sulfonamides (sulfa drugs) and the metals like mercury, copper, and silver bear antimicrobial properties. The discovery of broad-spectrum antibiotics such as penicillins, cephalosporins, and fluoroquinolones has reduced their use. However, in some instances these drugs are the first-line treatment. The metal-based sulfonamide (e.g., silver sulfadiazine) is considered as first choice treatment in post-burn therapy while the use of silver nanoparticle-cephalexin conjugate to cure Escherichia coli infection explains the synergistic effect of sulfa drugs and their metal conjugates. With growing interest in metal-based sulfonamides and the Schiff base chemistry, it was decided to synthesize sulfonamide Schiff base metal complexes as antioxidant and antimicrobial agent. Results The Fe (III), Ru (III), Co (II), Ni (II), Cu (II), Pd (II), Zn (II), Cd (II), and Hg (II) metal complexes of 4-((thiophen-2-ylmethylene)-amino)-benzenesulfonamide (TMABS) were prepared and studied for thermal stability, geometry, and other electronic properties. The ligand TMABS (Schiff base) and its metal complexes were screened in-vitro for 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and antimicrobial properties against Gram-positive (+ve) Bacillus subtilis (MTCC-441), Staphylococcus aureus (MTCC 7443), Gram-negative (-ve) Escherichia coli (MTCC 40), Salmonella typhi (MTCC 3231), and fungal strains Aspergillus niger (MTCC-1344) and Penicillium rubrum by agar well diffusion method. Results summarized in Tables 3, 4, and 5 represent the inhibitory concentration (IC50) in micromole (μM). The zone of inhibition (ZI) in millimeter (mm) represents antimicrobial properties of TMABS and its metal complexes. Conclusions The synthesized sulfanilamide Schiff base (TMABS) behaved as a neutral and bidentate ligand coordinating with metal ions through its azomethine nitrogen and thiophene sulfur to give complexes with coordination number of 4 and 6 (Fig. 3). The nucleophilic addition of sulfanilamide amino group (–NH2) group to carbonyl carbon (&gt;C=O) of benzaldehyde gave sulfanilamide Schiff base (imine) (Fig. 2). All the metal complexes were colored and stable at room temperature. With IC50 of 9.5 ± 0.1 and 10.0 ± 0.7 μM, the Co, Cu, and Pd complexes appeared better antioxidant than the ligand TMABS (155.3±0.1 μM). The zone of inhibition (ZI) of Hg (28 mm) and Ru complexes (20 mm) were similar to the ligand TMABS (20 mm) against Aspergillus niger (MTCC-1344) as in Figs. 4, 5, and 6. None of the synthesized derivatives had shown better antimicrobial properties than the standard streptomycin sulfate and fluconazole.


Synthesis, molecular docking, and preliminary cytotoxicity study of some novel 2-(naphthalen-1-yl)-methylimidazo[2,1-b][1,3,4]thiadiazoles
Choodamani B, Sujeet Kumar, Alok Kumar Gupta, Dominique Schols, Hakan Tahtaci, Tuncay Karakurt, Satvik Kotha, Swapna B, Ramachandra Setty, and Subhas S. Karki
Elsevier BV



Qualitative and Quantitative Study of Intermolecular Interactions in Imidazo[2,1-b] [1,3,4] Thiadiazoles
Ammankallu Sowmya, Gudibande N. A. Kumar, Sujeet Kumar and S. Karki




Synthesis, Molecular Docking and Preliminary Antileukemic Activity of 4-Methoxybenzyl Derivatives Bearing Imidazo[2,1-b][1,3,4]thiadiazole
B. Choodamani, Karla G. Cano Hernandez, Sujeet Kumar, Ann Maria Tony, Austre Y. Schiaffino Bustamante, Renato J. Aguilera, Dominique Schols, C. Gopi Mohan, and Subhas S. Karki
Wiley
In this study, we synthesized 22 compounds in a series with various substitution on imidazo[2,1‐b][1,3,4]thiadiazole. The potential cytotoxic activity of these compounds investigated in leukemia cell lines by Differential Nuclear Staining (DNS). Our results identified two compounds, 2‐(4‐methoxybenzyl)‐6‐(2‐oxo‐2H‐chromen‐3‐yl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl thiocyanate and 6‐(4‐chlorophenyl)‐2‐(4‐methoxybenzyl)imidazo[2,1‐b][1,3,4]thiadiazole‐5‐carbaldehyde, exhibited the most cytotoxic effect against murine leukemia cells (L1210), human T‐lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) with IC50 values ranging between 0.79 and 1.6 μM. The results indicate that 2‐(4‐methoxybenzyl)‐6‐(2‐oxo‐2H‐chromen‐3‐yl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl thiocyanate is inducing phosphatidylserine externalization and caspase‐3 activation which are both a hallmark of apoptosis. Docking studies showed that 2‐(4‐methoxybenzyl)‐6‐(2‐oxo‐2H‐chromen‐3‐yl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl thiocyanate binds within the active sites of transforming growth factor beta (TGF‐β) type I receptor kinase domain by strong hydrogen binding and hydrophobic interactions.


Synthesis, in silico ADME, molecular docking and in vitro cytotoxicity evaluation of stilbene linked 1,2,3-triazoles
Arnika Das, Sujeet Kumar, Leentje Persoons, Dirk Daelemans, Dominique Schols, Hakan Alici, Hakan Tahtaci, and Subhas S. Karki
Elsevier BV



St09, a novel curcumin derivative, blocks cell migration by inhibiting matrix metalloproteases in breast cancer cells and inhibits tumor progression in eac mouse tumor models
Snehal Nirgude, Raghunandan Mahadeva, Jinsha Koroth, Sujeet Kumar, Kothanahally S. Sharath Kumar, Vidya Gopalakrishnan, Subhas S Karki, and Bibha Choudhary
MDPI AG
Purpose: Curcumin is known for its anticancer and migrastatic activity in various cancers, including breast cancer. Newer curcumin derivatives are being explored to overcome limitations of curcumin like low bioavailability, stability, and side effects due to its higher dose. In this study, the synthesis of ST09, a novel curcumin derivative, and its antiproliferative, cytotoxic, and migrastatic properties have been explored both in vitro and in vivo. Methods: After ST09 synthesis, anticancer activity was studied by performing standard cytotoxicity assays namely, lactate dehydrogenase (LDH) release assay, 3-(4, 5-dimethylthiazol-2-yl)-2–5-diphenyletrazolium bromide (MTT), and trypan blue exclusion assay. Annexin-FITC, cell cycle analysis using flow cytometry, and Western blotting were performed to elucidate cell death mechanisms. The effect on the inhibition of cell migration was studied by transwell migration assay. An EAC (Ehrlich Ascites carcinoma) induced mouse tumor model was used to study the effect of ST09 on tumor regression. Drug toxicity was measured using aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and flow-cytometry based lymphocyte count. Histological analysis was performed for assessment of any tissue injury post ST09 treatment. Results: ST09 shows an approximate 100-fold higher potency than curcumin, its parent compound, on breast tumor cell lines MCF-7 and MDA-MB231. ST09 arrests the cell cycle in a cell type-specific manner and induces an intrinsic apoptotic pathway both in vitro and in vivo. ST09 inhibits migration by downregulating matrix metalloprotease 1,2 (MMP1,2) and Vimentin. In vivo, ST09 administration led to decreased tumor volume in a mouse allograft model by boosting immunity with no significant drug toxicity. Conclusion: ST09 exhibits antiproliferative and cytotoxic activity at nanomolar concentrations. It induces cell death by activation of the intrinsic pathway of apoptosis both in vitro and in vivo. It also inhibits migration and invasion. This study provides evidence that ST09 can potentially be developed as a novel antitumor drug candidate for highly metastatic and aggressive breast cancer.


Odorless glutathione microneedle patches for skin whitening
Yechan Lee, Sujeet Kumar, Sou Hyun Kim, Keum-Yong Seong, Hyeseon Lee, Chaerin Kim, Young-Suk Jung, and Seung Yun Yang
MDPI AG
Glutathione is a natural anti-aging substance that prevents the oxidation of protein thiols from reactive oxygen species. In the pharmaceutical industry, reduced glutathione (GSH) has been widely used for skin whitening due to its ability to inhibit tyrosinase. However, its poor permeability and foul odor limit its use in skin applications. Herein, we report a GSH-loaded dissolving microneedle (MN) patch prepared with hyaluronic acid (HA) that enables enhanced permeation across the skin and reduces the foul odor of GSH. HA was selected to prepare odorless GSH solutions and used for MN fabrications as a carrier of GSH. GSH-loaded MN (GSH-MN) arrays prepared from MN-forming solution containing up to 10% GSH showed good pattern uniformity and appropriate mechanical properties for insertion into the skin. The GSH-MNs with a loading capacity of 17.4% dissolve within 10 min following insertion into porcine skin and release the loaded GSH without being oxidized. This new approach combines functional biopolymers to reduce the characteristic GSH odor and advanced transdermal delivery based on MN technology to enhance skin permeation without pain. We believe this technique could expand the application of GSH in many cosmeceutical fields.


Crystal structure, quantum chemical and theoretical charge density analysis of 5‑bromo-2-(4-methylbenzyl)-6-(4-nitrophenyl)imidazo[2,1-b][1,3,4] thiadiazole
A. Sowmya, G.N. Anil Kumar, Sujeet Kumar, and Subhas S. Karki
Elsevier BV



Investigation of anti-cancer and migrastatic properties of novel curcumin derivatives on breast and ovarian cancer cell lines
Jinsha Koroth, Snehal Nirgude, Shweta Tiwari, Vidya Gopalakrishnan, Raghunandan Mahadeva, Sujeet Kumar, Subhas S. Karki, and Bibha Choudhary
Springer Science and Business Media LLC
Abstract Background Curcumin is known for its multitude of medicinal properties, including anti-cancer and migrastatic activity. Efforts to overcome poor bioavailability, stability, and side effects associated with the higher dose of curcumin has led to the development of newer derivatives of curcumin. Thus, the focus of this study is to screen novel curcumin derivatives, namely ST03 and ST08, which have not been reported before, for their cytotoxicity and migrastatic property on cancer cells. Methods Anti-cancer activity of ST03 and ST08 was carried out using standard cytotoxicity assays viz., LDH, MTT, and Trypan blue on both solid and liquid cancer types. Flow cytometric assays and western blotting was used to investigate the cell death mechanisms. Transwell migration assay was carried out to check for migrastatic properties of the compounds. Results Both the compounds, ST03 and ST08, showed ~ 100 fold higher potency on liquid and solid tumour cell lines compared to its parent compound curcumin. They induced cytotoxicity by activating the intrinsic pathway of apoptosis in the breast (MDA-MB-231) and ovarian cancer cell lines (PA-1) bearing metastatic and stem cell properties, respectively. Moreover, ST08 also showed inhibition on breast cancer cell migration by inhibiting MMP1 (matrix metalloproteinase 1). Conclusion Both ST03 and ST08 exhibit anti-cancer activity at nanomolar concentration. They induce cell death by activating the intrinsic pathway of apoptosis. Also, they inhibit migration of the cancer cells by inhibiting MMP1 in breast cancer cells.


Crystal structure, quantum chemical and Hirshfeld surface analysis of substituted imidazo-thiadiazole-5-carbaldehyde
A. Sowmya, G.N. Anil Kumar, Sujeet Kumar, and Subhas S. Karki
Elsevier BV



Utility of thromboelastography versus routine coagulation tests for assessment of hypocoagulable state in patients undergoing cardiac bypass surgery
Seema Sharma, Sujeet Kumar, Prabhat Tewari, Shantanu Pande, and Manjula Murari
Medknow
Introduction: Peri-operative monitoring of coagulation is important to diagnose potential cause of hemorrhage, to manage coagulopathy and guide treatment with blood products in patients undergoing cardiac surgery with cardiopulmonary bypass. This study was done to evaluate usefulness of Thromboelastography (TEG) and routine coagulation tests (RCT) in assessing hemostatic changes and predicting postoperative bleeding in patients undergoing cardiac surgery with cardiopulmonary bypass. Methods: Fifty adult patients undergoing cardiac surgery with cardiopulmonary bypass were enrolled in this prospective study. Preoperative and post-operative samples were collected for routine coagulation tests and TEG. Regression analysis and test of significance using Pearson's correlation coefficient was performed to assess correlation between routine coagulation tests and corresponding TEG parameters .Regression analysis was done to study relation between blood loss at 24 hours and various coagulation parameters. Results: The Routine coagulation test i.e. PT, INR, APTT showed no significant correlation with corresponding TEG parameters in pre-operative samples. However platelet count significantly correlated (p = 0.004) with MA values in postoperative samples. A significant correlation (p = 0.001) was seen between fibrinogen levels and alpha angles as well as with MA in both baseline preoperative and postoperative samples. TEG parameters R time and MA in postoperative samples were the only parameters that predicted bleeders with fair accuracy. Conclusion: Though the techniques of RCT and TEG are different, a few RCT e.g. platelet count and fibrinogen correlated with corresponding TEG parameters i.e. MA and Alpha angle. TEG parameters (R time and MA in postoperative samples) were able to predict blood loss better than RCT.


Identification and characterization of novel ligase I inhibitors
Monica Pandey, Sujeet Kumar, Gunaseelan Goldsmith, Mrinal Srivastava, Santhini Elango, Mohammad Shameem, Dibyendu Bannerjee, Bibha Choudhary, Subhas S. Karki, and Sathees C. Raghavan
Wiley
The terminal step of ligation of single and/or double‐strand breaks during physiological processes such as DNA replication, repair and recombination requires participation of DNA ligases in all mammals. DNA Ligase I has been well characterised to play vital roles during these processes. Considering the indispensable role of DNA Ligase I, a therapeutic strategy to impede proliferation of cancer cells is by using specific small molecule inhibitors against it. In the present study, we have designed and chemically synthesised putative DNA Ligase I inhibitors. Based on various biochemical and biophysical screening approaches, we identify two prospective DNA Ligase I inhibitors, SCR17 and SCR21. Both the inhibitors blocked ligation of nicks on DNA in a concentration‐dependent manner, when catalysed by cell‐free extracts or purified Ligase I. Docking studies in conjunction with biolayer interferometry and gel shift assays revealed that both SCR17 and SCR21 can bind to Ligase I, particularly to the DNA Binding Domain of Ligase I with KD values in nanomolar range. The inhibitors did not show significant affinity towards DNA Ligase III and DNA Ligase IV. Further, addition of Ligase I could restore the joining, when the inhibitors were treated with testicular cell‐free extracts. Ex vivo studies using multiple assays showed that even though cell death was limited in the presence of inhibitors in cancer cells, their proliferation was compromised. Hence, we identify two promising DNA Ligase I inhibitors, which can be used in biochemical and cellular assays, and could be further modified and optimised to target cancer cells. © 2016 Wiley Periodicals, Inc.


Synthesis and cytotoxic evaluation of some 2-{4-[(2-oxo-1,2-dihydro-3h-indol-3-ylidene)methyl] phenoxy}-n-phenylacetamide




A novel resveratrol based tubulin inhibitor induces mitotic arrest and activates apoptosis in cancer cells
Elizabeth Thomas, Vidya Gopalakrishnan, Mahesh Hegde, Sujeet Kumar, Subhas S. Karki, Sathees C. Raghavan, and Bibha Choudhary
Springer Science and Business Media LLC
Resveratrol is one of the most widely studied bioactive plant polyphenols which possesses anticancer properties. Previously we have reported synthesis, characterization and identification of a novel resveratrol analog, SS28. In the present study, we show that SS28 induced cytotoxicity in several cancer cell lines ex vivo with an IC50 value of 3–5 μM. Mechanistic evaluation of effect of SS28 in non-small cell lung cancer cell line (A549) and T-cell leukemic cell line (CEM) showed that it inhibited Tubulin polymerization during cell division to cause cell cycle arrest at G2/M phase of the cell cycle at 12–18 h time period. Immunofluorescence studies confirmed the mitotic arrest upon treatment with SS28. Besides, we show that SS28 binds to Tubulin with a dissociation constant of 0.414 ± 0.11 μM. Further, SS28 treatment resulted in loss of mitochondrial membrane potential, activation of Caspase 9 and Caspase 3, leading to PARP-1 cleavage and finally cell death via intrinsic pathway of apoptosis. Importantly, treatment with SS28 resulted in regression of tumor in mice. Hence, our study reveals the antiproliferative activity of SS28 by disrupting microtubule dynamics by binding to its cellular target Tubulin and its potential to be developed as an anticancer molecule.


Identification of a novel BCL2-specific inhibitor that binds predominantly to the BH1 domain
Divyaanka Iyer, Supriya V. Vartak, Archita Mishra, Gunaseelan Goldsmith, Sujeet Kumar, Mrinal Srivastava, Mahesh Hegde, Vidya Gopalakrishnan, Mark Glenn, Mahesh Velusamy,et al.
Wiley
The antiapoptotic protein BCL2 is overexpressed in several cancers and contributes to prolonged cell survival and chemoresistance, lending itself as an excellent target for cancer therapy. Here, we report the design, synthesis, and characterization of Disarib, a novel BCL2 inhibitor. Disarib showed selective cytotoxicity in BCL2 high cancer cell lines, and CLL patient primary cells, as compared to BCL2 low cell lines. BCL2 knockdown in cells rendered remarkable resistance to Disarib, while sensitivity was regained upon its ectopic expression, establishing target specificity. In silico, biochemical and biophysical studies demonstrated strong affinity of Disarib to BCL2, but not to other antiapoptotic BCL2 family members viz., BCL‐xL, BCL2A1 etc. Interestingly, biophysical studies showed that BH1 domain deletion mutant demonstrated ~ 67‐fold reduction in BCL2‐Disarib interaction, while it was only ~ 20‐fold in the case of BH3 deletion mutant, suggesting predominant involvement of the BH1 domain for Disarib binding. Thus, we report identification of a novel BCL2 inhibitor with a unique mechanism of BCL2 inhibition, as opposed to the well‐studied BH3 domain targeting.


Synthesis of stilbene-based resveratrol analogs as cytotoxic agents

RECENT SCHOLAR PUBLICATIONS

Synthesis, molecular docking, dynamics study and preliminary cytotoxicity study of some coumarin linked imidazothiadiazoles
S Kumar, PV Sravani, S Gokulakrishnan, S Khushwah, B Metikurki, ...
Journal of Molecular Structure 1321, 139943 2025



Dysfunctional mitochondrial bioenergetics sustains drug resistance in cancer cells
D Gnocchi, D Nikolic, S Russo, ML Matrella, RR Paparella, S Kumar, ...
American Journal of Physiology-Cell Physiology 2025



Investigation of Anti-Cancer Properties of Novel Curcuminoids in Leukemic Cells and Dalton Lymphoma Ascites Model
SS Karki, PS Vijayalakshmi Sudarshan, S Kumar, B Choudhary, ...
2025



Analyses of the optical and impedance characteristics of solution-casted Sod-Carboxy Methyl Cellulose Biodegradable Polymers prepared with a NaI/KI Blend
S Nalina, S Kumar, T Bhat, V Prakruthi, NS Keerthana, SS Pattanshetty, ...
2024



Discovery of new pyrazole-4-carboxamide analogues as potential anticancer agents targeting dual Aurora kinase A and B
Digambar Yevale, Nishith Teraiya, Twinkle Lalwani, Mayur Dalasaniya, Saumya ...
European Journal of Medicinal Chemistry, 116917 2024



Synthesis, In silico Study and Cytotoxicity Evaluation of Some Newly Synthesized Stilbene Derivatives
Dimple Pirgal, Subhas S. Karki, Sujeet Kumar, Basavraj Metikurki
Asian Journal of Chemistry 36 (8), 1882-1888 2024



Statistical modeling, optimization and characterization of andrographolide loaded emulgel for its therapeutic application on skin cancer through enhancing its skin permeability
M Sirisha, S Kumar, D Moumita, GD Rajesh, P Kumar
Saudi Pharmaceutical Journal 32 (2024), 102068 2024



Abstract 2396 Novel Ligase 1 and 4 Inhibitor Compounds as Potential Drugs for Cancer Treatment
GT Quesada, L Sanchez-Michael, D Gutierrez, A Varela-Ramirez, P Jain, ...
Journal of Biological Chemistry 300 (3) 2024



PP053 SP11, a promising coumarin-imidazothiadiazole derivative, targets HSP90 and client proteins to inhibit tumor growth
MV Shahana, S Nirgude, F Ravindran, S Kumar, S Sharma, R Mahadeva, ...
ESMO Open 8 (1) 2023



Enhancing the Thermoelectric Power Factor by Lowering the Electrical Resistivity of Bi₂Se₃/NaI Composites Prepared by Solid-State Reaction
Vivekananda, PK Prarthana, M Archana, R Gowrishree, T Bhat, ...
Journal of Electronic Materials 52 (12), 8076-8085 2023



Synthesis of novel pyrazole-oxindole conjugates with cytotoxicity in human cancer cells via apoptosis
Subhas S Karki, Pravesh J, Gutierrez D A, Kumar S, Aguilera R J
Chemistry & Biodiversity 2023



A Coumarin–Imidazothiadiazole Derivative, SP11 Abrogates Tumor Growth by Targeting HSP90 and Its Client Proteins
Nirgude S, Shahana M. V., Ravindran R, Kumar S, Sharma S, Mahadeva R, Mhatre ...
Molecules 28 (5226), 1-23 2023



Pyrazole Derivatives with Anticancer Activity
Renato J Aguilera, Subhas S Karki, Sujeet Kumar, Manuel L Penichet
US Patent App. 17/964,110 2023



Radioactive isotope-labeled photocross linkable hydrogel and preparation method therefor
Seung Yun Yang, Sodam Kim, San-gu Yim, Sujeet Kumar, Ajeesh Chandrasekharan
US Patent PCT/KR2019/018,094 2022



Synthesis, in vitro cytotoxicity, molecular docking and ADME study of some indolin-2-one linked 1, 2, 3-triazole derivatives
A Das, G Greco, S Kumar, E Catanzaro, R Morigi, A Locatelli, D Schols, ...
Computational Biology and Chemistry 97, 107641 2022



Novel Inhibitors of Antiapoptotic BCL-2 Proteins
Raghavan, S.C., Karki, S.S., Chaudhary, B., Surolia, A., Vartak, S., Iyer, D ...
IN Patent 386,398 2022



Synthesis, characterization, and biological evaluation of some 4-((thiophen-2-yl-methylene)amino)benzenesulfonamide metal complexes
EV Sekhar, SS Karki, J Rangaswamy, M Bhat, S Kumar
Beni-Suef University Journal of Basic and Applied Sciences 10, 1-9 2021



Synthesis, molecular docking, and preliminary cytotoxicity study of some novel 2-(naphthalen-1-yl)-methylimidazo [2, 1-b][1, 3, 4] thiadiazoles
B Choodamani, S Kumar, AK Gupta, D Schols, H Tahtaci, T Karakurt, ...
Journal of Molecular Structure 1234, 130174 2021



Synthesis, molecular docking, and preliminary cytotoxicity study of some novel 2-(naphthalen-1-yl)-methylimidazo [2, 1-b][1, 3, 4] thiadiazoles
S Kumar, AK Gupta, D Schols, H Tahtaci, T Karakurt, S Kotha, R Setty, ...
Journal of Molecular Structure 1234, 130174 2021



Qualitative and Quantitative Study of Intermolecular Interactions in Imidazo [2, 1‐b][1, 3, 4] Thiadiazoles
A Sowmya, GNA Kumar, S Kumar, SS Karki
ChemistrySelect 6 (17), 4265-4272 2021

MOST CITED SCHOLAR PUBLICATIONS

An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression
M Srivastava, M Nambiar, S Sharma, SS Karki, G Goldsmith, M Hegde, ...
Cell 151 (7), 1474-87 2012
Citations: 438



Synthesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4′-fluorophenyl)-imidazo [2, 1-b][1, 3, 4] thiadiazole derivatives as potent anticancer agents
SS Karki, K Panjamurthy, S Kumar, M Nambiar, SA Ramareddy, ...
European journal of medicinal chemistry 46 (6), 2109-16 2011
Citations: 139



A Novel Resveratrol Based Tubulin Inhibitor Induces Mitotic Arrest and Activates Apoptosis in Cancer Cells.
E Thomas, V Gopalakrishnan, M Hegde, S Kumar, SS Karki, SC Raghavan, B Choudhary
Scientific Reports 6, 34653 2016
Citations: 78



Novel levamisole derivative induces extrinsic pathway of apoptosis in cancer cells and inhibits tumor progression in mice
M Hegde, SS Karki, E Thomas, S Kumar, K Panjamurthy, ...
PloS one 7 (9), e43632 2012
Citations: 65



Investigation of anti-cancer and migrastatic properties of novel curcumin derivatives on breast and ovarian cancer cell lines.
Koroth J, Nirgude S, Tiwari S, Gopalakrishnan V, Mahadeva R, Kumar S, Karki ...
BMC Complementary and Alternative Medicine 19 (273), 1-16 2019
Citations: 56



Identification of a novel BCL2-specific inhibitor that binds predominantly to the BH1 domain.
NK D Iyer, SV Vartak, A Mishra, G Goldsmith, S Kumar, M Srivastava, M Hegde ...
The FEBS Journal 283, 3408-3437 2016
Citations: 51



2-(4-Chlorobenzyl)-6-arylimidazo [2, 1-b][1, 3, 4] thiadiazoles: synthesis, cytotoxic activity and mechanism of action
S Kumar, M Hegde, V Gopalakrishnan, VK Renuka, SA Ramareddy, ...
European journal of medicinal chemistry 84, 687-697 2014
Citations: 44



Synthesis and antiproliferative activity of imidazo [2, 1-b][1, 3, 4] thiadiazole derivatives
S Kumar, V Gopalakrishnan, M Hegde, V Rana, SS Dhepe, ...
Bioorganic & Medicinal Chemistry Letters 24 (19), 4682-4688 2014
Citations: 43



ST09, a novel curcumin derivative, blocks cell migration by inhibiting matrix metalloproteases in breast cancer cells and inhibits tumor progression in EAC mouse tumor models
S Nirgude, R Mahadeva, J Koroth, S Kumar, KSS Kumar, ...
Molecules 25 (19), 4499 2020
Citations: 37



Synthesis, anticancer and cytostatic activity of some 6H-indolo [2, 3-b] quinoxalines
S Karki, R Hazare, S Kumar, V Bhadauria, J Balzarini, E DeClercq
Acta Pharmaceutica 59 (4), 431 2009
Citations: 36



Odorless glutathione microneedle patches for skin whitening.
SY Lee, Y., Kumar, S., Kim, S.H., Seong, K.Y., Lee, H., Kim, C., Jung, Y.S ...
Pharmaceutics 12 (2), 1-12 2020
Citations: 34



Microwave-assisted synthesis and antimicrobial activity of some imidazo [2, 1-b][1, 3, 4] thiadiazole derivatives
S Dhepe, S Kumar, R Vinayakumar, SA Ramareddy, SS Karki
Medicinal Chemistry Research 21, 1550-1556 2012
Citations: 30



Synthesis and evaluation of the biological activity of N'-[2-oxo-1,2 dihydro-3H-indol-3-ylidene] benzohydrazides as potential anticancer agent.
SSK Arpit Katiyar,Mahesh Hegde, Sujeet Kumar, Vidya Gopalakrishnan, Khyati D ...
RSC Advances 5, 45492-501 2015
Citations: 25



1-Arylmethyl-2, 3-dioxo-2, 3-dihydroindole thiosemicarbazones as leads for developing cytotoxins and anticonvulsants
SS Karki, VS Bahaduria, V Rana, S Kumar, PG Subbaro, U Das, ...
Journal of enzyme inhibition and medicinal chemistry 24 (2), 537-544 2009
Citations: 23



Parameters controlling strength of red mud-lime mix
S Kumar, A Prasad
European Journal of Environmental and Civil Engineering 23 (6), 743-757 2019
Citations: 22



A neural network model for slope stability computations
S Kumar, PK Basudhar
Gotechnique Letters 8 (2), 149-154 2018
Citations: 22



Identification and characterization of novel ligase I inhibitors
M Pandey, S Kumar, G Goldsmith, M Srivastava, S Elango, M Shameem, ...
Molecular carcinogenesis 56 (2), 550-566 2017
Citations: 21



Synthesis and antimicrobial activity of some 3-substituted-2-oxindole derivatives
SS Karki, R Hazare, S Kumar, A Saxena, A Katiyar
Turk. J. Pharm. Sci 8, 169-178 2011
Citations: 13



Water-Soluble Version of SCR7-Pyrazine Inhibits DNA Repair and Abrogates Tumor Cell Proliferation
Pandey M, Gopalakrishnan V, Hassan SA, Kumar S, Gudapureddy R, Elizabeth JA ...
Journal of Radiation and Cancer Research 10, 27-43 2019
Citations: 12



Size fractionation of brown fly ash: Utilisation of grey fraction as a pozzolanic material in blended cement
S Kumar, JNY Djobo, A Kumar, S Kumar
European Journal of Environmental and Civil Engineering 24 (6), 833-848 2020
Citations: 11

GRANT DETAILS

UGC sponsored project (Diary KABA023/UGCSWRO, dated 28-3-2014 (₹ 1,85,000.00).

AICTE sponsored Research Promotion Scheme, F. No. 8023/BOR/RID/RP S-103/ 2009-10 dated 2211-2010 (₹ 14,30,000.00).

RESEARCH OUTPUTS (PATENTS, SOFTWARE, PUBLICATIONS, PRODUCTS)

Indian Patent filed (as co-inventor), Title: Novel inhibitors of anti-apoptotic BCL-2 Proteins.

US Patent filed (as co-inventor), Title: Pyrazole derivatives with anticancer activity.