Synthesis and In-silico Study of Novel 1,3,4-Oxadiazole Derivatives : A Biologically active Scaffolds which induce Anti-tubercular activity by targeting Pteridine Reductase and Dihydrofolate Reductase

Arti S. Jadhav; Akshay R. Yadav; Dr. Shrinivas K. Mohite

doi:10.32628/IJSRST229630

Authors

Arti S. Jadhav Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy, Kasegaon, Sangli, Maharashtra, India
Akshay R. Yadav Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy, Kasegaon, Sangli, Maharashtra, India
Dr. Shrinivas K. Mohite Department of Pharmaceutical Chemistry, Rajarambapu College of Pharmacy, Kasegaon, Sangli, Maharashtra, India

DOI:

https://doi.org//10.32628/IJSRST229630

Keywords:

1,3,4-oxadiazole derivatives, Microwave irradiation, Mycobacterium tuberculosis Almar dye method, Anti-tubercular activity.

Abstract

Heterocyclic compounds possess diverse biological properties that have led to intense study and research of these compounds. One of these compounds is Oxadiazole which has been found to exhibit various pharmacological activities. 1,3,4-oxadiazole having heterocyclic nucleus is a novel molecule which attract the chemist to search a new therapeutic molecule. Research on 1,3,4-oxadiazole and their synthetic analogues have revealed a variety of pharmacological activities including anti-microbial, anti-tubercular and insecticidal agents. Some of these compounds have also analgesic, anti-inflammatory, anti-cancer, anti-HIV agent, anti-parkinsonian and anti-proliferative agent. It was our interested to make novel derivatives of the titled compounds and evaluate the anti-tubercular activities. 1,3,4-oxadiazole and its derivatives (4a-4e) were obtained. The current study discusses the microwave irradiation synthesis of derivatives with the goal of generating new medications with high specificity for mycobacterium tuberculosis and low harm to the human.

References

Bala S, Kamboj S, Kumar A. Heterocyclic 1,3,4-oxadiazole compounds with diverse biological activities: A comprehensive review. J. Pharm. Res. 2010, vol.3(12), p.2993-2997.
Glomb T, Świątek P. Antimicrobial activity of 1, 3, 4-oxadiazole derivatives. Int J Mol Sci. 2021, vol.22(13), p.6971-6979.
Chikhalia KH, Vashi DB, Patel MJ. Synthesis of a novel class of some 1, 3, 4-oxadiazole derivatives as antimicrobial agents. J Enzyme Inhibition Med Chem. 2009, vol.24(3), p.617-622.
Yar MS, Siddiqui AA, Ashraf Ali M. Synthesis and Anti Tuberculostatic Activity of Novel 1,3,4‐Oxadiazole Derivatives. J Chinese Chem Soc. 2007, vol.54(1), p.5-8.
Ahsan MJ, Samy JG, Khalilullah H, Nomani MS, Saraswat P, Gaur R, Singh A. Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents. Bioorg Med Chem lett. 2011, vol. 21(24), p.7246-7250.
Dewangan D, Pandey A, Sivakumar T, Rajavel R, Dubey RD. Synthesis of some novel 2, 5-disubstituted 1,3,4-oxadiazole and its analgesic, anti-inflammatory, anti-bacterial and anti-tubercular activity. Int. J. Chem. Tech. Res. 2010, vol. 2(3), p.1397-412.
Raval JP, Akhaja TN, Jaspara DM, Myangar KN, Patel NH. Synthesis and in vitro antibacterial activity of new oxoethylthio-1, 3, 4-oxadiazole derivatives. J Saudi Chem Soc. 2014; vol.18(2), p.101-106.
Desai, N.C, Somani, H., Trivedi, A., Bhatt, K., Nawale, L., Khedkar, V.M., Jha, P.C., Sarkar, D., Synthesis, biological evaluation and molecular docking study of some novel indole and pyridine based 1,3,4-oxadiazole derivatives as potential antitubercular agents. Bioorg Med Chem Lett. 2016, vol.18(4), p.1-22.
Kapale, S.S., Mali, S.N. and Chaudhari, H.K., Molecular modelling studies for 4-oxo-1,4-dihyfroquinoline-3-carboxamide derivatives as anticancer agents. Med. Drug Disco., 2019, vol. 2, p. 100008.
Mali, S.N., Tambe, S., Pratap, A.P. and Cruz, J.N., Molecular Modeling Approaches to Investigate Essential Oils (Volatile Compounds) Interacting with Molecular Targets, Essential Oils. Springer, 2022, vol. 1, p.417-442.
Rout, S., Tambe, S., Deshmukh, R.K., Mali, S., Cruz, J., Srivastav, P.P., Amin, P.D., Gaikwad, K.K., de Aguiar Andrade, E.H. and de Oliveira, M.S., Recent trends in the application of essential oils: The next generation of food preservation and food packaging, Trends in Food Sci. Technol, 2022, vol.129, p. 421-439.
Mali, S.N. and Pandey, A., Molecular Modeling Studies on 2,4-Disubstituted Imidazopyridines as Anti-Malarials: Atom-Based 3D-QSAR, Molecular Docking, Virtual Screening, In-Silico ADMET and Theoretical Analysis, J. Comput. Biophys. Chem., 2021, vol. 20, p.267-282.
Ghosh, S., Mali, S.N., Bhowmick, D.N. and Pratap, A.P., Neem oil as natural pesticide: Pseudo ternary diagram and computational study, J Indian Chem. Soc., 2021, vol. 98, p.100088.
Mali, S.N., Pandey, A., Thorat, B.R. and Lai, C.H., Multiple 3D- and 2D-quantitative structure–activity relationship models (QSAR), theoretical study and molecular modeling to identify structural requirements of imidazopyridine analogues as anti-infective agents against tuberculosis, Structural Chemistry, 2022, vol. 33, p.679-694.
Bondock S, Adel S, Etman HA, Badria FA. Synthesis and antitumor evaluation of some new 1, 3, 4-oxadiazole-based heterocycles. European J Med Chem. 2012, vol. 48, p.192-199.
Stecoza CE, Nitulescu GM, Draghici C, Caproiu MT, Olaru OT, Bostan M, Mihaila M. Synthesis and anticancer evaluation of new 1,3,4-oxadiazole derivatives. Pharmaceuticals. 2021,vol.14(5), p.431-438.
Khalil NA, Kamal AM, Emam SH. Design, synthesis, and antitumor activity of novel 5-pyridyl-1,3,4-oxadiazole derivatives against the breast cancer cell line MCF-7. Biol. Pharm Bulletin. 2015, vol 38(5), p.763-73.
Ragab FA, Abou-Seri SM, Abdel-Aziz SA, Alfayomy AM, Aboelmagd M. Design, synthesis and anticancer activity of new monastrol analogues bearing 1, 3, 4-oxadiazole moiety. European J Med Chem. 2017, vol 29, p.140-151.
Mali, S.N. and Pandey, A., Balanced QSAR and Molecular Modeling to Identify Structural Requirements of Imidazopyridine Analogues as Anti-infective Agents Against Trypanosomiases, J. Comput. Biophys. Chem., 2022, vol. 21, p.83-114.
Anuse D , Thorat B , Sawant S , Yamgar R, Chaudhari H , Mali S. Synthesis, SAR, Molecular modeling docking and anti-microbial study of substituted N-bromoamido-2-aminobenzthiazoles. Curr Comput Aided Drug Des. 2020, vol.16(5), p.530-540.
Mali, S.N., Pandey, A., Bhandare, R.R. and Shaik, A.B., Identification of hydantoin based Decaprenenylphosphoryl-β-D-Ribose Oxidase (DprE1) inhibitors as antimycobacterial agents using computational tools, Sci. rep., 2022, vol. 12(1), p.1-21.
Thorat, B.R., Mali, S.N., Rani, D. and Yamgar, R.S., Synthesis, In silico and in vitro Analysis of Hydrazones as Potential Antituberculosis Agents, Curr. Comput.-Aided Drug Des, 2021, vol. 17, p.294-306.