Prof. Venkatesh Chelvam will give a lecture on December 15th 2021 at 14:00 in the Marie-Curie room.
Synthesis of Natural Products, Heterocycles and Small Molecule Inhibitors to Target Cancer, Inflammatory and Infectious Diseases
Prof. Dr. Venkatesh Chelvam Associate Professor
Department of Chemistry, and Department of Biosciences & Biomedical Engineering Indian Institute of Technology Indore, email: cvenkat@iiti.ac.in
A recent study conducted by International Agency for Research on Cancer in 2018 states that
there will be 18.1 million new cancer cases and 9.6 million cancer deaths worldwide. It has been
estimated that 27 million people would be diagnosed for cancer by 2030 resulting in 17 million deaths
every year [1]. This is partially attributed to tobacco use and high-fat diets, but a lack of early detection
and diagnostic methods is an indirect cause for cancer related mortality and morbidity. Among the
causation agents for infectious diseases, Mycobacterium tuberculosis (Mtb) infects one third of the
world’s population resulting in more than 1.5 million deaths every year globally. The treatment of TB is
further worsened after the emergence of multidrug resistant (MDR) and extremely drug resistant (XDR)
Mtb strains, which makes most of the available anti-TB drugs ineffective [2a]. According to the WHO report, an estimated 480,000 new MDR-TB and an additional 100,000
rifampicin-resistant TB (RR-TB) cases were reported. Among them, 50% cases are estimated to occur in
China and India. The current anti-TB regime involves six to nine months long administration of cocktail
of antibiotics. However, in case of MDR and XDR-TB the treatment duration varies from several
months to years with second line toxic drugs and rates of failure and mortality is very high. Mtb also
form “biofilms” responsible for increased drug tolerance and chronic TB disease [2b]. Altogether in the
present scenario, successful treatment of MDR and XDR-TB are very low. Therefore, there is a need to
develop new drugs with potent therapeutic applications. We have been working on synthesis of small
molecule inhibitors, natural products & their derivatives and heterocycles for the treatment of cancers
[3-9] and infectious diseases [10]. Many of these techniques are patented [11-13] and are at present in
various stages of preclinical development for treating cancer and infectious diseases. The present talk
will give an overview and research that has been carried out to improve the targeted delivery techniques
to for early detection and treatment of cancer, inflammatory and infectious diseases.
References:
1. (a) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide
for 36 cancers in 185 countries. CA Cancer J Clin. 2018, 68, 394–424. (b) World Cancer Report
2008. Lyon, France: International Agency for Research on Cancer; Boyle P, Levin B, editors.
2008.
2. (a)WHO Global Tuberculosis report, 2018. (b)Solokhina, A., Brückner, D., Bonkat, G.,
Braissant, O. (2017). Metabolic activity of mature biofilms of Mycobacterium tuberculosis and
other non-tuberculous mycobacteria. Sci Rep. 7(1), 9225.
3. Tyrosine-based asymmetric urea ligand for prostate carcinoma: Tuning biological efficacy
through in silico studies, Sengupta, S., Krishnan, M. A., Pandit, Amit, Dudhe, P., Sharma, R.,
Venkatesh C., Bioorganic Chem., 2019, 91, 103154. 4. Structure activity relationships (SAR) study to design and synthesis new tubulin inhibitors with
enhanced anti-tubulin activity: In silico Approach, Pandit, A., Reddy, R. B., Sengupta, S.,
Sharma, R., Venkatesh C., J. Mol. Struct., 2021, 1223, 129204. 5. A targeted near-infrared nanoprobe for deep-tissue penetration and imaging of prostate cancer,
Krishnan M.A., Yadav K., Roach P., Venkatesh C., Biomater Sci. 2021, 9, 2295. 2
6. Synthesis of the deacetoxytubuvaline (dTuv) fragment of pretubulysin and its lipophilic
analogues for enhanced permeability in cancer cell lines, Reddy, B. R., Dudhe, P., Venkatesh,
C., Synlett, 2019, 30, 77–81. 7. Comparison of prostate specific membrane antigen ligands in clinical translation research for
diagnosis of prostate cancer. Sengupta, S., Krishnan, M, Chattopadhyay, S., Venkatesh, C.,
Cancer Reports., 2019, 1-22. 8. Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: One pot metal-solvent free protocol and
biological evaluation; Dudhe, P., Krishnan, M.A., Yadav, K., Roy, D., Venkatasubbaiah, K.,
Pathak, B., Chelvam, V., Beilstein J. Org. Chem., 2021, 17, 1453. 9. (a) Developing μSpherePlatform Using a commercial hairbrush: An agarose 3D culture platform
for deep-tissue imaging of prostate cancer, Krishnan M.A., Venkatesh C., ACS Appl Bio Mater.
2021, 4, 4254. (b) Imaging of prostate cancer: Optimizing affinity to prostate specific membrane
antigen by spacer modifications in a tumor spheroid model, Krishnan M.A., Pandit A., Sharma
R., Venkatesh C. J. Biomol Struct Dyn. 2021, Jun 27, 1-22 (in press). 10. Serendipitous base catalysed condensation-heteroannulation of iminoesters: A regioselective
route to synthesis of 4,6-disubstituted 5-azaindoles, Org. Biomol. Chem., 2020, 18, 1582–1587. 11. New small molecule inhibitors/ligands for early diagnosis and therapy of prostate specific
membrane antigen (PSMA+) cancers and neurodegenerative diseases, Sengupta, S., Krishnan, M.
A., Pandit, A., Venkatesh, Chelvam, Nov. 2018, Indian patent, Application no. 201821044594;
Nov. 2019, USA Patent, Application no. 16695851. 12. Method and system for metal-free solvent-free synthesis of fused-pyrido heterocycles and their
biological activities against cancer and multi-drug resistant pathogens, Venkatesh, C., Dudhe, P.,
Krishnan, M. A., Sonawane, A., July 2019, Indian Patent, Application no. 201921029311; 2020,
USA Patent, Application no. 2021/0070765 A1. 13. Third generation tubulysin analogues and process of preparation thereof, Venkatesh Chelvam,
Amit Pandit, Ramesh B. Reddy, Kratika Yadav, Diptendu Roy, Biswarup Pathak, Aug. 2020,
Indian Patent, Application No. 202021036140; Mar. 2021, USA Patent, Application No.
17/198,918.