Dr.SREEKANTH THOTA
@nipswgl.in
PROFESSOR, PHARMACEUTICAL CHEMISTRY & ANALYSIS
NETHAJI INSTITUTE OF PHARMACEUTICAL SCIENCES
I currently serve as a Professor at the NETHAJI INSTITUTE OF PHARMACEUTICAL SCIENCES located in Kazipet, Warangal, Telangana, India. My academic journey began with a Bachelor's degree in Pharmacy from Kakatiya University, Warangal, India, followed by a Master's degree in Pharmacy from Rajiv Gandhi University of Health Sciences in Bangalore, India. Subsequently, I earned my PhD from Jawaharlal Nehru Technological University Hyderabad in 2011.
In recognition of my research endeavors, I was honored with the Research Promotion Scheme award sponsored by AICTE, New Delhi in 2012. Furthering my academic pursuits, I pursued postdoctoral research at Colorado State University in the USA during 2013. I was honored with the CAPES-Fiocruz Visiting Researcher award in 2013 and worked as a Visiting Research Scientist at CDTS-Fiocruz & LASSBio (UFRJ), Brazil from 2014 to 2018. My research focus is on Drug discovery, Drug design, and Medicinal chemistry with over 45 publications.
EDUCATION
Education: Jawaharlal Nehru Technological University of Hyderabad, Hyderabad, Telangana, India.
Ph.D. in (Pharmaceutical Sciences), 2007-2011
Advisor: Prof. Subhas S Karki
Rajiv Gandhi University of Health Sciences, Bengaluru, Karnataka, India.
M. Pharmacy-Pharmaceutical Chemistry, 2004-2006
Kakatiya University, Warangal, Telangana, India.
B. Pharmacy, 1999-2003
RESEARCH, TEACHING, or OTHER INTERESTS
Drug Discovery, Biochemistry, Genetics and Molecular Biology, Chemistry, Cancer Research
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Daniel A. Rodrigues, Pedro de Sena M. Pinheiro, Fernanda S. Sagrillo, Maria Clara R. Freitas, Marina A. Alves, Sreekanth Thota, Luzineide W. Tinoco, Alvicler Magalhães, Carlos M. R. Sant’Anna, and Carlos A. M. Fraga
Royal Society of Chemistry (RSC)
A serendipitous identification and characterization of a new non-classical hydrogen bond donor moiety found in N-acylhydrazones containing 3-acyl-substituted furan subunit is presented.
Daniel A. Rodrigues, Fabiana S. Guerra, Fernanda S. Sagrillo, Pedro de Sena M. Pinheiro, Marina A. Alves, Sreekanth Thota, Lorrane S. Chaves, Carlos M. R. Sant'Anna, Patrícia D. Fernandes, and Carlos A. M. Fraga
Wiley
AbstractTargeting histone deacetylases (HDACs) and phosphatidylinositol 3‐kinases (PI3Ks) is a very promising approach for cancer treatment. This manuscript describes the design, synthesis, in vitro pharmacological profile, and molecular modeling of a novel class of N‐acylhydrazone (NAH) derivatives that act as HDAC6/8 and PI3Kα dual inhibitors. The surprising selectivity for PI3Kα may be related to differences in the conformation in the active site. Cellular studies showed that these compounds act in HDAC6 inhibition and the PI3/K/AKT/mTOR pathway. The compounds that are selective for inhibition of HDAC6/8 and inhibit PI3Kα show potential for the treatment of cancer.
Pedro de Sena M. Pinheiro, Daniel A. Rodrigues, Rodolfo do Couto Maia, Sreekanth Thota, and Carlos A.M. Fraga
Bentham Science Publishers Ltd.
During the early preclinical phase, from hit identification and optimization to a lead compound, several medicinal chemistry strategies can be used to improve potency and/or selectivity. The conformational restriction is one of these approaches. It consists of introducing some specific structural constraints in a lead candidate to reduce the overall number of possible conformations in order to favor the adoption of a bioactive conformation and, as a consequence, molecular recognition by the target receptor. In this work, we focused on the application of the conformational restriction strategy in the last five years for the optimization of hits and/or leads of several important classes of therapeutic targets in the drug discovery field. Thus, we recognize the importance of several kinase inhibitors to the current landscape of drug development for cancer therapy and the use of G-protein Coupled Receptor (GPCR) modulators. Several other targets are also highlighted, such as the class of epigenetic drugs. Therefore, the possibility of exploiting conformational restriction as a tool to increase the potency and selectivity and promote changes in the intrinsic activity of some ligands intended to act on many different targets makes this strategy of structural modification valuable for the discovery of novel drug candidates.
Sreekanth Thota, Daniel A. Rodrigues, Pedro de Sena Murteira Pinheiro, Lídia M. Lima, Carlos A.M. Fraga, and Eliezer J. Barreiro
Elsevier BV
Sreekanth Thota, Daniel A. Rodrigues, Debbie C. Crans, and Eliezer J. Barreiro
American Chemical Society (ACS)
Metal based therapeutics are a precious class of drugs in oncology research that include examples of theranostic drugs, which are active in both diagnostic, specifically imaging, and therapeutics applications. Ruthenium compounds have shown selective bioactivity and the ability to overcome the resistance that platinum-based therapeutics face, making them effective oncotherapeutic competitors in rational drug invention approaches. The development of antineoplastic ruthenium therapeutics is of particular interest because ruthenium containing complexes NAMI-A, KP1019, and KP1339 entered clinical trials and DW1/2 is in preclinical levels. The very robust, conformationally rigid organometallic Ru(II) compound DW1/2 is a protein kinase inhibitor and presents new Ru(II) compound designs as anticancer agents. Over the recent years, numerous strategies have been used to encapsulate Ru(II) derived compounds in a nanomaterial system, improving their targeting and delivery into neoplastic cells. A new photodynamic therapy based Ru(II) therapeutic, TLD-1433, has also entered clinical trials. Ru(II)-based compounds can also be photosensitizers for photodynamic therapy, which has proven to be an effective new, alternative, and noninvasive oncotherapy modality.
Daniel Alencar Rodrigues, Pedro de Sena Murteira Pinheiro, Thayssa Tavares da Silva Cunha Ferreira, Sreekanth Thota, and Carlos Alberto Manssour Fraga
Wiley
G‐protein‐coupled receptor 40 (GPR40) was recently identified as an interesting target for treatment of type 2 diabetes. The high level of expression in pancreatic beta cells and the dependence of glucose on stimulating the secretion of insulin led to great excitement in this field. The identification of this target was followed by the development of a series of agonists with great potential for the treatment of diabetes. All known agonists have the presence of a pharmacophoric carboxylic acid group in their structure, which makes several polar interactions at the binding site of this receptor. In this report, we provide a review of the structure–activity relationships of GPR40 agonists with a focus on the main strategies of medicinal chemistry used to develop each one of the main structural patterns exploited for this purpose. Additionally, we provide a general model for the design of GPR40 ligands that can help researchers to follow up some strategies and implement them in the development of novel agonists of this receptor.
Sreekanth Thota, Daniel Alencar Rodrigues, and Eliezer J. Barreiro
Bentham Science Publishers Ltd.
Still now, for many forms of the disseminated cancers there is no curative therapy available. The discovery of novel active chemotherapeutic agents is largely essential to overcome this problem. Natural compounds polyphenols are mainly characterized by a huge structural variance; they can render them intrinsic dietary components due to their common occurrence in plants. Now-a-days, polyphenols (secondary metabolites) are characterized by a vast spectrum of physiological significance. From the past twenty years in the world of scientific research, polyphenols play an important role in a wide range of physiological processess. This review focuses on the development of polyphenols as antitumor agent in recent research studies.
Sreekanth Thota and Carlos M. Morel
Bentham Science Publishers Ltd.
Chagas disease is caused by the parasite Trypanosoma cruzi and is regularly found among particular people living in Central and South America. Paediatric Chagas disease occurs in 1-10% of infants of infected mothers. The major important point considered in the treatment of congenital Chagas disease focuses on killing the parasite in acute infection and managing signs and symptoms in later stages. Nowadays, two drugs benznidazole and nifurtimox are currently available in the market for the treatment of paediatric Chagas disease.
Sundeep Kadasi, Thadeu E.M.M. Costa, Neha Arukala, Mallika Toshakani, Chaitanya Duggineti, Sreekanth Thota, Sayan D. Gupta, Shiva Raj, Carmen Penido, Maria G. Henriques,et al.
Bentham Science Publishers Ltd.
BACKGROUND
Heat shock protein 90 is a molecular chaperone required for the stability and function of several client proteins that promote cancer cell growth and/or survival. Discovery of Hsp90 inhibitors has emerged as an attractive target of research in cancer therapeutics. Natural products like geldanamycin and radicicol are established Hsp90 inhibitors, but face limitations with toxicity and inactivity, by in vivo studies respectively. However, they lay the logical starting point for the design of novel synthetic or semi-synthetic congeners as Hsp90 inhibitors.
OBJECTIVE
In this article, the structure based drug design of substituted 2-aryl/heteroarylidene-6- hydroxybenzofuran-3(2H)-one analogues to optimize and mimic the pharmacophoric interactions of the valid Hsp90 inhibitor radicicolis focused.
METHOD
In silico docking study was performed by Surflex dock-Geom (SYBYL- X 1.2 drug discovery suite) and the designed ligands were chemically synthesized by conventional method using resorcinol and chlororesorcinol as starting materials. Two dimensional chemical similarity search was carried out to identify the chemical space of 'SY' series in comparison with reported Hsp90 inhibitors. The in vitro cell proliferation assay (resazurin reduction method) and proteomic investigation (DARTS) was carried out on whole cell lysate to evaluate anticancer activity.
RESULTS
The chemical structures of all the synthesized compounds were confirmed by IR, 1H-NMR and Mass spectral analysis. The results of chemical similarity search show that SY series fit it in the chemical space defined by existing Hsp90 inhibitors. In vitro cell proliferation assay, against human melanoma and breast cancer cell lines, identified 'SY3' as the promising anticancer agent amongst the series.
CONCLUSION
Docking studies, 2D chemical similarity search, resazurin reduction assay and qualitative proteomic analysis identify 'SY3'as a promising Hsp90 inhibitor amongst the series.
Sreekanth Thota, Srujana Vallala, Rajeshwar Yerra, Daniel Alencar Rodrigues, and Eliezer J. Barreiro
Springer Science and Business Media LLC
Daniel A. Rodrigues, Sreekanth Thota, and Carlos A.M. Fraga
Bentham Science Publishers Ltd.
Histone deacetylase 6 (HDAC6) catalyses the removal of acetyl groups from the lysine residues of a series of non-histone proteins, e.g., α-tubulin, Hsp90 and cortactin. HDAC6 is a unique deacetylase enzyme that is related to various processes that may be important in oncological, immunological and neurological fields, which makes the study of selective inhibitors extremely important to understand the function of this enzyme and to validate HDAC6 as a drug target through the development of clinical candidates. Therefore, this review describes the structure-activity and structureselectivity relationships of HDAC6 inhibitors, which were divided into two main classes, bulky and lipophilic cap groups and inhibitors with phenyl linkers.
Sreekanth Thota
Bentham Science Publishers Ltd.
Sreekanth Thota and Rajeshwar Yerra
Bentham Science Publishers Ltd.
Malaria, a deadly infectious parasitic disease, is a major issue of public health in the world today and already produces serious economic constraints in the endemic countries. Most of the malarial infections and deaths are due to Plasmodium falciparum and Plasmodium vivax species. The recent emergence of resistance necessitates the search for new antimalarial drugs, which overcome the resistance and act through new mechanisms. Although much effort has been directed towards the discovery of novel antimalarial drugs. 4-anilino quinolone triazines as potent antimalarial agents, their in silico modelling and bioevaluation as Plasmodium falciparum transketolase and β-hematin inhibitors has been reported. This review is primarily focused on the drug discovery of the recent advances in the development of antimalarial agents and their mechanism of action.
Sreekanth Thota, Srujana Vallala, Rajeshwar Yerra, Daniel Alencar Rodrigues, Nulgumnalli Manjunathaiah Raghavendra, and Eliezer J. Barreiro
Elsevier BV
Sreekanth Thota and Carlos Morel
Bentham Science Publishers Ltd.
Diseases started even before the existence of human beings. Therefore, when the civilization began, the biggest threats for human were diseases. Man has made several sincere attempts for the search of new drugs in order to cure and control different diseases. Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that accounts for about 85-95% of all diagnosed cases of diabetes. It is characterized by abnormalities in glucose homeostasis in many organs, and is associated with considerable morbidity and mortality. Extensive research has been carried out using rational drug design to identify and optimize new leads for molecular targets of T2DM, which include Heterocyclic compounds, metal complexes, H3 receptor antagonists, glucagon receptor antagonists and human incretin-degrading enzyme dipeptidyl peptidase IV inhibitors.
Sreekanth Thota, Kavitha Nadipelly, Anusha Shenkesi, and Rajeshwar Yerra
Springer Science and Business Media LLC
Sreekanth Thota, Srujana Vallala, Rajeshwar Yerra, and Eliezer J. Barreiro
Elsevier BV
Kiran Gangarapu, Sarangapani Manda, Anvesh Jallapally, Sreekanth Thota, Subhas S. Karki, Jan Balzarini, Erik De Clercq, and Harukuni Tokuda
Springer Science and Business Media LLC
Sreekanth Thota, Srujana Vallala, Mohammad Imran, Sravani Mekala, Shyam Sunder Anchuri, Subhas Somalingappa Karki, Rajeshwar Yerra, Jan Balzarini, and Erik De Clercq
Informa UK Limited
New mononuclear Ru(II) complexes [Ru(A)2(B)]2+, where A = 2,2′-bipyridine/1,10-phenanthroline and B = 3,4,5-tri-OCH3-DPC, 4-CH3-DPC, 4-N(CH3)2-DPC, 4-NO2-DPC, N-BITSZ, PTSZ and PINH, were prepared and characterized by spectroscopic methods. The in vitro cytotoxic activities of the complexes and their corresponding ligands were investigated against the human cancer T-lymphocyte cell lines molt 4/c8 and CEM and the murine tumor leukemia cell line L1210, human promyelocytic leukemia cells (HL-60) and Bel-7402 liver cancer cells by MTT assay. The complexes [Ru(A)2(B)]2+ (A = 1,10-phenanthroline, B = 3,4,5-tri-OCH3-DPC) exerts rather more potent activities against all of these cell lines, especially for CEM and L1210. Ru complexes and structure–activity relationships and anticancer mechanisms are also discussed.
Shyam Sunder Anchuri, Sreekanth Thota, Raja Narender Bongoni, Rajeshwar Yerra, Rama Narsimha Reddy, and Satyavati Dhulipala
Wiley
AbstractThe present work was aimed that the two Ruthenium compounds namely, [Ru(A)2(B)]Cl2, where A = 1,10‐phenanthroline; B = 2‐NO2‐phenyl thiosemicarbazone (Compound R1)/2‐OH‐phenyl thiosemicarbazone (Compound R2) have been tested for antibacterial activity at the concentrations of 1 mg/mL against various Gram‐Positive organisms (Lactobacillus, Staphylococcus pyrogenes, Bacillus subtilis, Staphylococcus aureus & Bacillus megatarium) and Gram‐Negative organisms (Pseudomonas aeruginosa, Escherichia coli, Proteus vulgaris, Enterobacter aerogenes, Salmonella paratyphi, Klebsiella pneumonia & Proteus mirabilis). The compounds were also tested for antifungal activity against Aspergillus clavatus, Aspergillus niger, Colletotrichum & Penicillium notatum by using agar diffusion assay and antimalarial activity against Plasmodium falciparum (Strain 3D7) using MTT assay. The results concluded that the compound R1 exhibited significant antibacterial activity than R2 against Gram‐Negative bacteria with zones of inhibition ranging from 15‐20 mm. and mild antibacterial activity against Gram‐Positive bacteria in comparison to tetracycline, streptomycin and rifampicin. These complexes were found to have moderate antifungal activity with no activity was however observed against Aspergillus niger. The compound, R1 exhibited antimalarial activity at 10 μg/mL, whereas R2 did not show antimalarial activity upto 50 μg/mL. Sensitivity to the compounds was greatest in the gram‐negative bacteria, followed by the gram‐positive bacteria and fungi.
Kiran Gangarapu, Sarangapani Manda, Sreekanth Thota, Rajeshwar Yerra, Subhas S. Karki, Jan Balzarini, Erik De Clercq, and Harukuni Tokuda
Bentham Science Publishers Ltd.
RECENT SCHOLAR PUBLICATIONS
MOST CITED SCHOLAR PUBLICATIONS
Publications
Books & Book Chapters:
1. Thota S, Crans DC. “Metal Nanoparticles: Synthesis and Applications in Pharmaceutical Sciences”
Wiley-VCH Verlag GmbH & Co. KGaA, Germany, 2018, ISBN: 978-3-527-33979-2. Direct Link
2. Thota S, Crans DC. Introduction: “Metal Nanoparticles: Synthesis and Applications in Pharmaceutical Sciences”
Wiley-VCH Verlag GmbH & Co. KGaA, Germany, 2018, Book Chapter, Direct Link
Research Publications (In peer-reviewed journals):
1. Rodrigues DA, Pinheiro PSM, Sagrillo FS, Ramalho-Freitas MC, Alves MA, Thota S, Tinoco L, Magalhães A, Sant'Anna, CMR, Fraga CAM. Structure-Property Relationship Studies of 3-Acyl-Substituted Furans: The Serendipitous Identification and Characterization of a New Non-Classical Hydrogen Bond Donor Moiety. New J Chem. 2020; 44: 10994-11005. Direct Link
2. Rodrigues DA, Guerra FS, Sagrillo FS, Pinheiro PSM, Alves MA, Thota S, Chaves LS, Sant’Anna CMR, Fernandes PD, Fraga
CAM. Design, Synthesis and Pharmacological Evaluation of First‐in‐Class Multitarget N‐Acylhydrazone Derivatives as Selective HDAC6/8 and PI3Kα Inhibitors. Chem Med Chem. 2020; 15(6): 539-551. Direct Link
3. Kadasi S, Costa TEMM, Arukala, N, Toshakani M, Duggineti C, Thota S, Gupta SD, Raj S, Penido C, Henriques MG, Raghavendra NM. “Drug design, synthesis and in vitro evaluation of substituted benzofurans as Hsp90 inhibitors’’ Med Chem. 2018; 14(1): 44-52. Direct Link
4. Thota S, Vallala S, Yerra R, Rodrigues DA, Raghavendra NM, Barreiro EJ. "
GRANT DETAILS
2014 CAPES-Fiocruz Senior Postdoctoral Researcher award grant, Fiocruz, Rio de Janeiro, Brazil
2013 Research Scholar, Colorado state University, Colorado, USA
2011 Research Promotion Scheme grant, AICTE, New Delhi, India
Industry, Institute, or Organisation Collaboration
Collaborative Research:
Professional Appointments:
January-2023 to till date Professor, Nethaji Institute of Pharmaceutical Sciences, Warangal (T.S).
August-2018 to December-2022 Professor, Tirumala College of Pharmacy, Nizamabad, Telanagana.
16th September-2014 to 9th August-2018 Visiting Researcher, Fiocruz & UFRJ, Rio de Janeiro, Brazil.
2013-2014 Associate Professor, S. R. College of Pharmacy, Kakatiya University, Warangal, India.
2013 Research Scholar, Colorado State University, Colorado, Fort Collins, USA.
2010-2013 Associate Professor, S. R. College of Pharmacy, Kakatiya University, Warangal, India.
2008-2010 Assistant Professor, S. R. College of Pharmacy, Kakatiya University, Warangal, India.
2006-201. INCT-IDN, National Institute of Science and Technology of innovation in neglected diseases. Rio de Janeiro, Brazil.
2. National Institute of Health, Bethesda, USA.
3. Prof. Eliezer J. Barreiro, LASSBio, UFRJ, Cidade Universitaria, Rio de Janeiro, Brazil.
4. Prof. Dr. Erick De Clercq, Rega Institute for Medical Research, minderbroedersstraat, 10, B-3000, Leuven, Belgium.
5. Prof. Debbie C Crans, Department of Chemistry, Colorado State University, USA.