DEVELOPMENT OF NOVEL 1, 3, 4-THIADIAZOLES AS ANTITUBERCULAR AGENTS-SYNTHESIS AND IN VITRO SCREENING

ANCY THOMAS; VINOD B.; SNEHA SHENOY K. U.; VISHNU M. V.

doi:10.22159/ijcpr.2023v15i3.3009

Authors

ANCY THOMAS National College of Pharmacy, Mukkam, Kozhikkode, Kerala, India
VINOD B. St Joseph’s College of Pharmacy, Dharmagiri Campus, Cherthala, Kerala, India
SNEHA SHENOY K. U. St Joseph’s College of Pharmacy, Dharmagiri Campus, Cherthala, Kerala, India
VISHNU M. V. Chemists College of Pharmacy, Varikoli, Puthencruz, Kerala, India

DOI:

https://doi.org/10.22159/ijcpr.2023v15i3.3009

Keywords:

Tuberculosis, Mycobacterium tuberculei, 1,3,4-thiadiazole, Alamar blue, Minimum inhibitory concentration

Abstract

Objective: Tuberculosis, known in short as TB, is considered to be a global crisis caused by Myco bacterium tuberculosis, and which continues to be a serious challenge to public health world wide especially in the developing countries. A serious problem related to tuberculosis is the development of drug resistant strains.

Methods: Present study describes the synthesis of eight novel derivatives of 1,3,4-thiadiazole derivatives and in vitro evaluation of their anti tubercular activity against Mycobacterium tuberculosis H37 Rv strain by alamar blue assay. Pyrazinamide and Streptomycin were the standards, used for the evaluation.

Results: Among the eight compounds synthesized one derivative was found to be active against the strain tested. All the other derivatives tested exhibited negligible activity against the strain.

Conclusion: It can be concluded that novel 1, 3, 4-thiadiazole derivatives can be developed as novel agents in the fight against TB.

Downloads

Download data is not yet available.

References

Cinu TA, Sidhartha SK, Indira B, Varadaraj BG, Vishnu PS, Shenoy GG. Design, synthesis and evaluation of antitubercular activity of Triclosan analogues. Arab J Chem. 2019;12(8):3316-23. doi: 10.1016/j.arabjc.2015.09.003.

Global Tuberculosis Repot; 2020. Available from: www.who/int/i/item/9789240013131.

Coxon GD, Craig D, Corrales RM, Vialla E, Gannoun Zaki L, Kremer L. Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues. PLOS ONE. 2013;8(1):e53162. doi: 10.1371/journal.pone.0053162. PMID 23301038.

Nguyen L. Antibiotic resistance mechanisms in M. tuberculosis: an update. Arch Toxicol. 2016;90(7):1585-604. doi: 10.1007/s00204-016-1727-6, PMID 27161440.

Bandodkar B, Shandil RK, Bhat J, Balganesh TS. Two decades of TB drug discovery efforts-what have we learned? Appl Sci. 2020;10(16):5704. doi: 10.3390/app10165704.

Cherian B, Kumar RA, Vinod B. Pyrazole carbaldehydes as novel antiinflammatory agents. Synthesis and in vitro membrane stabilization method. J Pharm Sci Res. 2020;12(2):252-7.

Raj V, Rai A, Singh AK, Keshari AK, Trivedi P, Ghosh B. Discovery of novel 2-Amino-5-(Substituted)-1,3,4-Thiadiazole derivatives: new utilities for colon cancer treatment. Anticancer Agents Med Chem. 2018;18(5):719-38. doi: 10.2174/1871520617666170419122916, PMID 28425852.

Eskandari D, Zou D, Grote L, Hoff E, Hedner J. Acetazolamide reduces blood pressure and sleep-disordered breathing in patients with hypertension and obstructive sleep apnea: a randomized controlled trial. J Clin Sleep Med. 2018;14(3):309-17. doi: 10.5664/jcsm.6968, PMID 29510792.

Millichap JG, Millichap JJ. Mechanism of action of acetazolamide and idiopathic intracranial hypertension. Front Neurol. 2015;6(13):1. doi: 10.3389/fneur.2015.00013.

Shlim DR. The use of acetazolamide for the prevention of high-altitude illness. J Travel Med. 2020 Aug 06;27:taz106. doi: 10.1093/jtm/taz106, PMID 31897486.

Nunez J, Heredia R, Paya A, Sanchis I, Del Prado S, Minana G. Use of acetazolamide in the treatment of patients with refractory congestive heart failure. Cardiovasc Ther. 2018;36(6):e12465. doi: 10.1111/1755-5922.12465, PMID 30191652.

Serban G, Stanasel O, Serban E, Bota S. 2-Amino-1,3,4-thiadiazole as a potential scaffold for promising antimicrobial agents. Drug Des Devel Ther. 2018;12:1545-66. doi: 10.2147/DDDT.S155958. PMID 29910602.

Tahghighi A, Babalouei F. Thiadiazoles: the appropriate pharmacological scaffolds with leishmanicidal and antimalarial activities: a review. Iran J Basic Med Sci. 2017;20(6):613-22. doi: 10.22038/IJBMS.2017.8828, PMID 28868117.

Akhter MW, Hassan MZ, Amir M. Synthesis and pharmacological evaluation of 3-diphenylmethyl-6-substituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles: a condensed bridgehead nitrogen heterocyclic system. Arab J Chem. 2014;7(6):955-63. doi: 10.1016/j.arabjc.2014.05.036.

Sharma B, Verma A, Prajapati S, Sharma UK. Synthetic methods, chemistry, and the anticonvulsant activity of thiadiazoles. Int J Med Chem. 2013. doi: 10.1155/2013/348948, PMID 25405032.

Sharma B, Verma A, Prajapati S, Sharma UK. Synthetic methods, chemistry, and the anticonvulsant activity of thiadiazoles. International Journal of Medicinal Chemistry. 2013;2013:1-16. doi: 10.1155/2013/348948.

Szeliga M. Thiadiazole derivatives as anticancer agents. Pharmacol Rep. 2020;72(5):1079-100. doi: 10.1007/s43440-020-00154-7, PMID 32880874.

Datar PA. Design and synthesis of thiadiazole derivatives as antidiabetic agents. Med Chem. 2014;4(4). doi: 10.4172/2161-0444.1000170.

Sadat Ebrahimi SE, Mirmohammadi M, Mojallal Tabatabaei Z, Azimzadeh Arani M, Jafari Ashtiani S, Hashemian M. Novel 5-(nitrothiophene-2-yl)-1,3,4-thiadiazole derivatives: synthesis and antileishmanial activity against promastigote stage of Leishmania major. Iran J Pharm Res. 2019;18(4):1816-22. doi: 10.22037/ijpr.2019.14547.12476, PMID 32184848.

Gupta P, Bhatter P, D’souza D, Tolani M, Daswani P, Tetali P. Evaluating the anti Mycobacterium tuberculosis activity of Alpinia galanga (L.) Willd. Axenically under reducing oxygen conditions and in intracellular assays. BMC Complement Altern Med. 2014;14:84. doi: 10.1186/1472-6882-14-84, PMID 24592852.

Sonar VN, Crooks PA. Synthesis and antitubercular activity of a series of hydrazone and nitrovinyl analogs derived from heterocyclic aldehydes. J Enzyme Inhib Med Chem. 2009;24(1):117-24. doi: 10.1080/14756360801915526. PMID 18629678.