SUJEET KUMAR
@dr.sujeethkumar@nitte.edu.in
Professor-Pharmaceutical Chemistry/Pharmacy
Nitte College of Pharmaceutical Sciences (A constituent unit of Nitte Education Trust), Bengaluru
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
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
N. V. L. Sirisha Mulukuri, Sujeet Kumar, Moumita Dhara, Gupta Dheeraj Rajesh, and Pankaj Kumar
Elsevier BV
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
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.
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.
Arnika Das, Giulia Greco, Sujeet Kumar, Elena Catanzaro, R. Morigi, A. Locatelli, D. Schols, Hakan Alici, Hakan Tahtaci, Febina Ravindran,et al.
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 (>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.
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
Ammankallu Sowmya, Gudibande N. A. Kumar, Sujeet Kumar and S. Karki
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.
Arnika Das, Sujeet Kumar, Leentje Persoons, Dirk Daelemans, Dominique Schols, Hakan Alici, Hakan Tahtaci, and Subhas S. Karki
Elsevier BV
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.
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.
A. Sowmya, G.N. Anil Kumar, Sujeet Kumar, and Subhas S. Karki
Elsevier BV
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.
A. Sowmya, G.N. Anil Kumar, Sujeet Kumar, and Subhas S. Karki
Elsevier BV
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.
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.
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.
A. Sowmya, G. N. Anil Kumar, Sujeet Kumar, and Subhas S. Karki
International Union of Crystallography (IUCr)
In the title imidazo[2,1-b][1,3,4]thiadiazole derivative, C19H14ClN3OS, the 4-methylbenzyl and chlorophenyl rings are inclined to the planar imidazo[2,1-b][1,3,4]thiadiazole moiety (r.m.s. deviation = 0.012 Å) by 64.5 (1) and 3.7 (1)°, respectively. The molecular structure is primarily stabilized by a strong intramolecular C—H...O hydrogen bond, leading to the formation of a pseudo-seven-memberedS(7) ring motif, and a short intramolecular C—H...N contact forming anS(5) ring motif. In the crystal, molecules are linked by pairs of C—H...S hydrogen bonds, forming inversion dimers. The dimers are linked by C—H...O and C—H...π interactions, forming chains propagating along [110].
Arpit Katiyar, Mahesh Hegde, Sujeet Kumar, Vidya Gopalakrishnan, Khyati D. Bhatelia, Kavya Ananthaswamy, Sureshbabu A. Ramareddy, Erik De Clercq, Bibha Choudhary, Dominique Schols,et al.
Royal Society of Chemistry (RSC)
New N′-[2-oxo-1,2-dihydro-3H-indol-3-ylidene]benzohydrazide derivatives were synthesized and evaluated for their cytotoxic properties against murine leukemia, L1210, human leukemia, REH, K562 and CEM and human cervix carcinoma, HeLa cells.
RECENT SCHOLAR PUBLICATIONS
MOST CITED SCHOLAR PUBLICATIONS
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.