Login Register Cart 0
Generic placeholder image

Current Indian Science

Editor-in-Chief

ISSN (Print): 2210-299X
ISSN (Online): 2210-3007

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Research Article

ADME, Synthesis and Antimycobacterial Activity of 1,2,4-Triazol-3-thiol Linked Phenylacetamide Derivatives

Author(s): Trupti Chitre*, Shivani Jadhav, Kalyani Asgaonkar, Kunal Pradhan, Kalash Shelke, Shubhangi Thorat and Aniket Bhatambrekar

Volume 1, 2023

Published on: 08 November, 2023

Article ID: e2210299X239429 Pages: 7

DOI: 10.2174/012210299X239429231026060353

Price: $

Abstract

Background: Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is one of the most contagious and fatal human pathogens which necessitates the development of modified existing drugs or derivatives with action against novel targets.

Aims and Objectives: In the present work, we have explored a few, 2-(5-(substituted)-4H-1,2,4-triazole-2-ylthio)-N-(substituted) phenyl acetamide (5A-5E) derivatives as anti-TB.

Materials and Methods: On the basis of SAR were synthesized and screened against Mycobacterium tuberculosis H37Rv using MABA assay. Their ADME properties were also checked.

Results: ADME analysis showed results comparable with standard drug (rifampicin). Derivative 5D turned out to be the most active amongst all the derivatives with MIC of 0.8μg/ml, comparable to standard drugs like rifampicin(0.8μg/ml) and streptomycin(0.8μg/ml).

Conclusion: All five compounds have shown excellent inhibitory activity (1.6μg/ml) against the Mycobacterium tuberculosis H37Rv strain. Compound 5D shows a promising activity (0.8μg/ml) as compared to standard drugs and also it has shown the highest docking score. Literature search has revealed the presence of 1,2,4-triazole derivatives linked to aromatic link and possessing amide linkage and the presence of Sulphur atom in the most active derivatives, which supports our designed compounds. Based on these findings, further derivatives would be synthesized and explored for their role in tuberculosis.

[1]
Available from: https://www.who.int/teams/global-tuberculosis- programme/tb-reports/global-tuberculosis-report-2022 (Accessed on: 10/11/2022).
[2]
Harding, E. WHO global progress report on tuberculosis elimination. Lancet Respir. Med., 2020, 8(1), 19.
[http://dx.doi.org/10.1016/S2213-2600(19)30418-7] [PMID: 31706931]
[3]
Jeremiah, C.; Petersen, E.; Nantanda, R.; Mungai, B.N.; Migliori, G.B.; Amanullah, F.; Lungu, P.; Ntoumi, F.; Kumarasamy, N.; Maeurer, M.; Zumla, A. The WHO Global Tuberculosis 2021 Report-notso good news and turning the tide back to End TB. Int. J. Infect. Dis., 2022.
[4]
Rodrigues, L.; Cravo, P.; Viveiros, M. Efflux pump inhibitors as a promising adjunct therapy against drug resistant tuberculosis: A new strategy to revisit mycobacterial targets and repurpose old drugs. Expert Rev. Anti Infect. Ther., 2020, 18(8), 741-757.
[http://dx.doi.org/10.1080/14787210.2020.1760845] [PMID: 32434397]
[5]
Taghipour, A.; Azimi, T.; Javanmard, E.; Pormohammad, A.; Olfatifar, M.; Rostami, A.; Tabarsi, P.; Sohrabi, M.R.; Mirjalali, H.; Haghighi, A. Immunocompromised patients with pulmonary tuberculosis; a susceptible group to intestinal parasites. Gastroenterol. Hepatol. Bed Bench, 2018, 11(Suppl. 1), S134-S139.
[PMID: 30774820]
[6]
Seung, K.J.; Keshavjee, S.; Rich, M.L. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Cold Spring Harb. Perspect. Med., 2015, 5(9), a017863.
[http://dx.doi.org/10.1101/cshperspect.a017863] [PMID: 25918181]
[7]
Sarkar, D 1,2,4-triazole, 1,3,4-oxadiazole, and 1,3,4-thiadiazole derivatives and their antimycobacterial activity WIPO PCT. WO 2016/108249 A1, 2016.
[8]
Sarkar, S.; Swami, S.; Soni, S.K.; Holien, J.K.; Khan, A.; Korwar, A.M.; Likhite, A.P.; Joshi, R.A.; Joshi, R.R.; Sarkar, D. Detection of a target protein (GroEl2) in Mycobacterium tuberculosis using a derivative of 1,2,4-triazolethiols. Mol. Divers., 2022, 26(5), 2535-2548.
[http://dx.doi.org/10.1007/s11030-021-10351-y] [PMID: 34822095]
[9]
Karczmarzyk, Z.; Swatko-Ossor, M.; Wysocki, W.; Drozd, M.; Ginalska, G.; Pachuta-Stec, A.; Pitucha, M. New application of 1,2,4-Triazole derivatives as antitubercular agents. Structure, in vitro screening and docking studies. Molecules, 2020, 25(24), 6033.
[http://dx.doi.org/10.3390/molecules25246033] [PMID: 33352814]
[10]
Ganesh, N.; S, A.K.; Singh, M.; Chandrashekar, V.M.; Pujar, G.V. Antitubercular potential of novel isoxazole encompassed 1, 2, 4- Triazoles: Design, synthesis, molecular docking study and evaluation of antitubercular activity. Antiinfect. Agents, 2021, 19(2), 147-161.
[http://dx.doi.org/10.2174/2211352518999200711163714]
[11]
Seelam, N.; Shrivastava, S.P.; S, P.; Gupta, S. Synthesis and in vitro study of some fused 1,2,4-triazole derivatives as antimycobacterial agents. J. Saudi Chem. Soc., 2016, 20(4), 411-418.
[http://dx.doi.org/10.1016/j.jscs.2012.11.011]
[12]
Venugopala, K.N.; Kandeel, M.; Pillay, M.; Deb, P.K.; Abdallah, H.H.; Mahomoodally, M.F.; Chopra, D. Anti-Tubercular properties of 4-Amino-5-(4-Fluoro-3- Phenoxyphenyl)-4H-1,2,4-Triazole-3-Thiol and its schiff bases: Computational input and molecular dynamics. Antibiotics, 2020, 9(9), 559.
[http://dx.doi.org/10.3390/antibiotics9090559] [PMID: 32878018]
[13]
Zabiulla, S.; Al-Ostoot, F.; S, A.; Al-Ghorbani, M.; Khanum, S. Recent investigation on heterocycles with one nitrogen [piperidine, pyridine and quinoline], two nitrogen [1,3,4-thiadiazole and pyrazole] and threenitrogen [1,2,4-triazole]: A review. J. Iran. Chem. Soc., 2021, 1-32.
[14]
Mandewale, M.C.; Thorat, B.; Nivid, Y.; Jadhav, R.; Nagarsekar, A.; Yamgar, R. Synthesis, structural studies and antituberculosis evaluation of new hydrazone derivatives of quinoline and their Zn(II) complexes. J. Saudi Chem. Soc., 2018, 22(2), 218-228.
[http://dx.doi.org/10.1016/j.jscs.2016.04.003]
[15]
Karabanovich, G.; Dušek, J.; Savková, K.; Pavliš, O.; Pávková, I.; Korábečný, J.; Kučera, T.; Kočová Vlčková, H.; Huszár, S.; Konyariková, Z.; Konečná, K.; Jand’ourek, O.; Stolaříková, J.; Korduláková, J.; Vávrová, K.; Pávek, P.; Klimešová, V.; Hrabálek, A.; Mikušová, K.; Roh, J. Development of 3,5-Dinitrophenyl-Containing 1,2,4-Triazoles and their Trifluoromethyl analogues as highly efficient antitubercular agents inhibiting Decaprenylphosphoryl-β- D -ribofuranose 2′-Oxidase. J. Med. Chem., 2019, 62(17), 8115-8139.
[http://dx.doi.org/10.1021/acs.jmedchem.9b00912] [PMID: 31393122]
[16]
Somagond, S.M.; Kamble, R.R.; Bayannavar, P.K.; Shaikh, S.K.J.; Joshi, S.D.; Kumbar, V.M.; Nesaragi, A.R.; Kariduraganavar, M.Y. Click chemistry based regioselective one‐pot synthesis of coumarin‐3‐yl‐methyl‐1,2,3‐triazolyl‐1,2,4‐triazol‐3(4 H )‐ones as newer potent antitubercular agents. Arch. Pharm., 2019, 352(10), 1900013.
[http://dx.doi.org/10.1002/ardp.201900013] [PMID: 31397503]
[17]
Amado, P.S.M.; Woodley, C.; Cristiano, M.L.S.; O’Neill, P.M. Recent advances of DprE1 inhibitors against Mycobacterium tuberculosis : Computational analysis of physicochemical and ADMET properties. ACS Omega, 2022, 7(45), 40659-40681.
[http://dx.doi.org/10.1021/acsomega.2c05307] [PMID: 36406587]
[18]
Ganesh Kumar, T.N.V.; Gautham Shenoy, G.; Kar, S.S.; Shenoy, V.; Bairy, I. Design, synthesis and evaluation of antitubercular activity of novel 1,2,4-Triazoles against MDR strain of mycobacterium tuberculosis. Pharm. Chem. J., 2018, 51(10), 907-917.
[http://dx.doi.org/10.1007/s11094-018-1714-8]
[19]
Sonawane, A.D.; Rode, N.D.; Nawale, L.; Joshi, R.R.; Joshi, R.A.; Likhite, A.P.; Sarkar, D. Synthesis and biological evaluation of 1,2,4‐triazole‐3‐thione and 1,3,4‐oxadiazole‐2‐thione as antimycobacterial agents. Chem. Biol. Drug Des., 2017, 90(2), 200-209.
[http://dx.doi.org/10.1111/cbdd.12939] [PMID: 28083914]
[20]
Yan, M.; Xu, L.; Wang, Y.; Wan, J.; Liu, T.; Liu, W.; Wan, Y.; Zhang, B.; Wang, R.; Li, Q. Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents. Drug Dev. Res., 2020, 81(4), 402-418.
[http://dx.doi.org/10.1002/ddr.21638] [PMID: 31904877]
[21]
Vora, D.; Upadhyay, N.; Tilekar, K.; Jain, V.; Ramaa, C.S. Development of 1,2,4-Triazole-5-Thione derivatives as potential inhibitors of Enoyl Acyl Carrier Protein Reductase (InhA) in Tuberculosis. Iran. J. Pharm. Res., 2019, 18(4), 1742-1758.
[PMID: 32184843]
[22]
Zhang, S.; Xu, Z.; Gao, C.; Ren, Q.C.; Chang, L.; Lv, Z.S.; Feng, L.S. Triazole derivatives and their anti-tubercular activity. Eur. J. Med. Chem., 2017, 138, 501-513.
[http://dx.doi.org/10.1016/j.ejmech.2017.06.051] [PMID: 28692915]
[23]
Hosangadi, B.D.; Dave, R.H. An efficient general method for esterification of aromatic carboxylic acids. Tetrahedron Lett., 1996, 37(35), 6375-6378.
[http://dx.doi.org/10.1016/0040-4039(96)01351-2]
[24]
Chen, Z.; Xu, W.; Liu, K.; Yang, S.; Fan, H.; Bhadury, P.S.; Huang, D-Y.; Zhang, Y. Synthesis and antiviral activity of 5‑(4‑chlorophenyl)-1,3,4-thiadiazole sulfonamides. Molecules, 2010, 15(12), 9046-9056.
[http://dx.doi.org/10.3390/molecules15129046] [PMID: 21150824]
[25]
Kumar, P.; Narasimhan, B.; Yogeeswari, P.; Sriram, D. Synthesis and antitubercular activities of substituted benzoic acid N′-(substituted benzylidene/furan-2-ylmethylene)-N-(pyridine-3-carbonyl)-hydrazides. Eur. J. Med. Chem., 2010, 45(12), 6085-6089.
[http://dx.doi.org/10.1016/j.ejmech.2010.08.030] [PMID: 20828886]
[26]
Kostecka, M. Synthesis of a new group of aliphatic hydrazide derivatives and the correlations between their molecular structure and biological activity. Molecules, 2012, 17, 3560-3573.
[27]
Mali, R.; Somani, R.; Mp, T.; Mali, K.; Pp, N.; Py, S. Synthesis of some Antifungal and Anti-tubercular 1, 2, 4-Triazole Analogues. Int. J. Chemtech Res., 2009, 1, 168-173.
[28]
Parikh, K.; Joshi, D. Synthesis and evaluation of 2-(5-(aryl)-1,3,4-oxadiazol-2-ylthio)-N-(3-(trifluoromethyl)phenyl)acetamides and N-(4-chloro-3-fluorophenyl)-2-(5-(aryl)-1,3,4-oxadiazol-2-ylthio)acetamides as antimicrobial agents. J. Chem. Sci., 2014, 126(3), 827-835.
[http://dx.doi.org/10.1007/s12039-014-0625-9]
[29]
Nafeesa, K.; Aziz-ur-Rehman; Abbasi, M.; Zahra, S.; Rasool, S.; Shah, S.A. Synthesis, characterization and pharmacological evaluation of different 1,3,4-oxadiazole and acetamide derivatives of ethyl nipecotate. Bull. Fac. Pharm. Cairo Univ., 2017, 55.
[30]
Siddiqui, S.Z.; Abbasi, M.A.; Rehman, A.; Ashraf, M.; Mirza, B.; Ismail, H. Synthesis of 2-[(5-benzyl-1,3,4-oxadiazole-2yl)sulfanyl]-N-(arylated/arenylated) acetamides as antibacterial and acetyl cholinesterase inhibitors. Pak. J. Pharm. Sci., 2017, 30(5), 1743-1751.
[PMID: 29084697]
[31]
Available from:https://molsoft.com/mprop/
[32]
Srivastava, R. Theoretical studies on the molecular properties, toxicity, and biological efficacy of 21 new chemical entities. ACS Omega, 2021, 6(38), 24891-24901.
[http://dx.doi.org/10.1021/acsomega.1c03736] [PMID: 34604670]
[33]
Lourenço, M.C.S.; Souza, M.V.N.; Pinheiro, A.C.; Ferreira, M.L.; Gonçalves, R.S.B.; Nogueira, T.C.M.; Peralta, M.A.; Nogueira, C.; Peralta, M. Evaluation of anti-tubercular activity of nicotinic and isoniazid analogues. ARKIVOC, 2007, 2007(15), 181-191.
[http://dx.doi.org/10.3998/ark.5550190.0008.f18]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy