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Current HIV Research

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ISSN (Print): 1570-162X
ISSN (Online): 1873-4251

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Research Article

One-Pot Synthesis of Novel Hydrazono-1,3-Thıazolıdın-4-One Derivatives as Anti-HIV and Anti-Tubercular Agents: Synthesıs, Bıologıcal Evaluatıon, Molecular Modelling and Admet Studıes

Author(s): Mohammad Arif Pasha, Sumanta Mondal*, Naresh Panigrahi, Gauri Shetye, Rui Ma, Scott G. Franzblau, Yong-Tang Zheng and Sankaranarayanan Murugesan

Volume 20, Issue 3, 2022

Published on: 15 July, 2022

Page: [255 - 271] Pages: 17

DOI: 10.2174/1570162X20666220512163049

Price: $65

Abstract

Background: The necessity for newer anti-HIV and anti-tubercular medications has arisen as a result of the prevalence of opportunistic infections caused by HIV (human immunodeficiency virus).

Objective: A series of ten new hydrazono 1,3-thiazolidin-4-one derivatives were synthesized in one-pot and evaluated for anti-HIV and anti-tubercular activities. Molecular Docking was accomplished with HIV-1 reverse transcriptase protein (PDB ID: 1REV) and Mycobacterium Tuberculosis (M. tuberculosis) H37Rv protein (PDB ID: 2YES) receptors along with drug-likeness and ADMET properties.

Methods: One-pot synthesis of hydrazono 1,3-thiazolidin-4-one derivatives was carried out by ketones, thiosemicarbazide and ethylchloroacetate with the catalyst of anhydrous sodium acetate. All the synthesized compounds were characterized and evaluated for their in-vitro anti-HIV and also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis H37Rv. In-silico predicted physicochemical parameters were done by MedChem DesignerTM software version 5.5 and ADMET parameters by pkCSM online tool. Furthermore, molecular docking was performed with pyrx 0.8 by autodock vina software.

Results: All the synthesized compounds were characterized and evaluated for their in-vitro anti- HIV activity for inhibition of syncytia formation, which shows KTE1 with EC50 47.95 μM and Selectivity Index (SI) of >4.17 and for inhibition of p24 antigen production EC50 was found to be 80.02 μM and SI of >2.49. The compounds were also evaluated for their in-vitro anti-tubercular activity against M. tuberculosis H37Rv, in which KTE1 MIC values of 12.5μg/ml with SI of >4.0 and cytotoxicity against Vero cell lines. In-silico predicted physicochemical parameters for synthesized compounds which were found to be drug-like. Furthermore, docking has shown a good dock score and binding energy with anti-HIV and anti-tubercular receptors.

Conclusion: From the novel synthesized molecules, none of the molecule is as effective as standards for anti-HIV and anti-tubercular drugs and hence can be further explored for its potential activities. Furthermore, derivatization was made to achieve more potent compounds for anti-HIV and anti-tubercular drugs.

Keywords: Hydrazono 1, 3-thiazolidin-4-one, H37Rv, anti-HIV, anti-tubercular, ADMET.

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[1]
Esté JA, Cihlar T. Current status and challenges of antiretroviral research and therapy. Antiviral Res 2010; 85(1): 25-33.
[http://dx.doi.org/10.1016/j.antiviral.2009.10.007] [PMID: 20018390]
[2]
La Regina G, Coluccia A, Brancale A, et al. Indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: New cyclic substituents at indole-2-carboxamide. J Med Chem 2011; 54(6): 1587-98.
[http://dx.doi.org/10.1021/jm101614j] [PMID: 21366296]
[3]
Zanoni BC, Gandhi RT. Update on opportunistic infections in the era of effective antiretroviral therapy. Infect Dis Clin North Am 2014; 28(3): 501-18.
[http://dx.doi.org/10.1016/j.idc.2014.05.002] [PMID: 25151568]
[4]
Fernandes GFDS, Man Chin C, Dos Santos JL. Advances in drug discovery of new antitubercular multidrug-resistant compounds. Pharmaceuticals (Basel) 2017; 10(2): 51.
[http://dx.doi.org/10.3390/ph10020051] [PMID: 28587160]
[5]
World Health Organization. WHO policy on collaborative TB/HIV activities: Guidelines for nationalprogrammes and other stakeholders. Geneva: World Health Organization 2012; pp. 1-36. Available from: http://www.who.int/tb/publications/2012/tb_hiv_policy_ 978 9241503006/en/ (Accessed 22 March 2018).
[6]
Sahiba N, Sethiya A, Soni J, Agarwal DK, Agarwal S. Saturated five-membered thiazolidines and their derivatives: From synthesis to bio-logical applications. Top Curr Chem (Cham) 2020; 378(2): 34.
[http://dx.doi.org/10.1007/s41061-020-0298-4] [PMID: 32206929]
[7]
Singh SP, Parmar SS, Raman K, Stenberg VI. Chemistry and biological activity of thiazolidinones. Chem Rev 1981; 81(2): 175-203.
[http://dx.doi.org/10.1021/cr00042a003]
[8]
Devappa SL, Reddy KRV, Reddy KBGR, et al. A simple and efficient carbodiimide mediated one pot synthesis of novel 2-(2-hydroxynaphthalen-1-yl)-3-phenyl-1,3-thiazolidin-4one derivatives: A potent antimicrobial agent. Int J Chemtech Res 2010; 2(2): 1220-8.
[9]
Srinivas A, Nagaraj A, Reddy CS. Synthesis and in vitro study of methylene-bis-tetrahydro[1,3]thiazolo[4,5-c]isoxazoles as potential nematicidal agents. Eur J Med Chem 2010; 45(6): 2353-8.
[http://dx.doi.org/10.1016/j.ejmech.2010.02.014] [PMID: 20199825]
[10]
Ravichandran V, Jain A, Kumar KS, Rajak H, Agrawal RK. Design, synthesis, and evaluation of thiazolidinone derivatives as antimicrobial and anti-viral agents. Chem Biol Drug Des 2011; 78(3): 464-70.
[http://dx.doi.org/10.1111/j.1747-0285.2011.01149.x] [PMID: 21615706]
[11]
Vintonyak VV, Warburg K, Over B, Hübel K, Rauh D, Waldmann H. Identification and further development of thiazolidinones spiro-fused to indolin-2-ones as potent and selective inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B. Tetrahedron 2011; 67(35): 6713-29.
[http://dx.doi.org/10.1016/j.tet.2011.04.026]
[12]
Ravichandran V, Prashantha Kumar BR, Sankar S, Agrawal RK. Predicting anti-HIV activity of 1,3,4-thiazolidinone derivatives: 3D-QSAR approach. Eur J Med Chem 2009; 44(3): 1180-7.
[http://dx.doi.org/10.1016/j.ejmech.2008.05.036] [PMID: 18687505]
[13]
Kato T, Ozaki T, Ohi N. Improved synthetic methods of CP-060S, a novel cardioprotective drug. Tetrahedron Asymmetry 1999; 10(20): 3963-8.
[http://dx.doi.org/10.1016/S0957-4166(99)00441-3]
[14]
Voss ME, Carter PH, Tebben AJ, et al. Both 5-arylidene-2-thioxodihydropyrimidine-4,6(1H,5H)-diones and 3-thioxo-2,3-dihydro-1H-imidazo[1,5-a]indol-1-ones are light-dependent tumor necrosis factor-α antagonists. Bioorg Med Chem Lett 2003; 13(3): 533-8.
[http://dx.doi.org/10.1016/S0960-894X(02)00941-1] [PMID: 12565966]
[15]
Agarwal A, Lata S, Saxena KK, Srivastava VK, Kumar A. Synthesis and anticonvulsant activity of some potential thiazolidinonyl 2-oxo/thiobarbituric acids. Eur J Med Chem 2006; 41(10): 1223-9.
[http://dx.doi.org/10.1016/j.ejmech.2006.03.029] [PMID: 16919852]
[16]
Bhati SK, Kumar A. Synthesis of new substituted azetidinoyl and thiazolidinoyl-1,3,4-thiadiazino (6,5-b) indoles as promising anti-inflammatory agents. Eur J Med Chem 2008; 43(11): 2323-30.
[http://dx.doi.org/10.1016/j.ejmech.2007.10.012] [PMID: 18063224]
[17]
Deep A, Jain S, Sharma PC, Phogat P, Malhotra M. Synthesis of 2-(aryl)-5-(arylidene)-4-thiazolidinone derivatives with potential analgesic and anti-inflammatory activity. Med Chem Res 2011; 21(8): 1652-9.
[http://dx.doi.org/10.1007/s00044-011-9679-0]
[18]
Schenck JR, De Rose AF. Actithiazic acid. II. Isolation and characterization. Arch Biochem Biophys 1952; 40(2): 263-9.
[http://dx.doi.org/10.1016/0003-9861(52)90110-0] [PMID: 12997211]
[19]
Sobin BA. A new streptomyces antibiotic. J Am Chem Soc 1952; 74(11): 2947-8.
[http://dx.doi.org/10.1021/ja01131a526]
[20]
Abdelall EKA, Kamel GM. Synthesis of new thiazolo-celecoxib analogues as dual cyclooxygenase-2/15-lipoxygenase inhibitors: Determi-nation of regio-specific different pyrazole cyclization by 2D NMR. Eur J Med Chem 2016; 118: 250-8.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.049] [PMID: 27131067]
[21]
Fischer W, Bodewei R, Satzinger G. Anticonvulsant and sodium channel blocking effects of ralitoline in different screening models. Naunyn Schmiedebergs Arch Pharmacol 1992; 346(4): 442-52.
[http://dx.doi.org/10.1007/BF00171088] [PMID: 1331817]
[22]
Greven J, Heidenreich O. Effects of ozolinone, a diuretic active metabolite of etozoline, on renal function. I. Clearance studies in dogs. Naunyn Schmiedebergs Arch Pharmacol 1978; 304(3): 283-7.
[http://dx.doi.org/10.1007/BF00507970] [PMID: 714186]
[23]
Krische D. The glitazones: Proceed with caution. West J Med 2000; 173(1): 54-7.
[http://dx.doi.org/10.1136/ewjm.173.1.54] [PMID: 10903299]
[24]
Bonne D, Coquerel Y, Constantieux T, Rodriguez J. 1,3-Dicarbonyl compounds in stereoselective domino and multicomponent reactions. Tetrahedron Asymmetry 2010; 21(9-10): 1085-109.
[http://dx.doi.org/10.1016/j.tetasy.2010.04.045]
[25]
Ugi I, Dömling A, Horl W. Multicomponent reactions in organic chemistry. Endeavour 1994; 18(3): 115-22.
[http://dx.doi.org/10.1016/S0160-9327(05)80086-9]
[26]
Desai NC, Dodiya A, Shihory N. Synthesis and antimicrobial activity of novel quinazolinone–thiazolidine–quinoline compounds. J Saudi Chem Soc 2013; 17(3): 259-67.
[http://dx.doi.org/10.1016/j.jscs.2011.04.001]
[27]
Jadhav SA, Shioorkar MG, Chavan OS, Chavan RV, Shinde DB, Pardeshi RK. An eco-friendly solvent free one pot multi-component syn-thesis of Coumarin thiazolidinone derivatives. Pharma Chem 2015; 7(5): 329-34.
[28]
Wang YH, Tang JG, Wang RR, et al. Flazinamide, a novel β-carboline compound with anti-HIV actions. Biochem Biophys Res Commun 2007; 355(4): 1091-5.
[http://dx.doi.org/10.1016/j.bbrc.2007.02.081] [PMID: 17336271]
[29]
Ashok P, Lu CL, Chander S, Zheng YT, Murugesan S. Design, synthesis, and biological evaluation of 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole derivatives as anti-HIV-1 agents. Chem Biol Drug Des 2015; 85(6): 722-8.
[http://dx.doi.org/10.1111/cbdd.12456] [PMID: 25328020]
[30]
Chander S, Ashok P, Zheng YT, et al. Design, synthesis and in-vitro evaluation of novel tetrahydroquinoline carbamates as HIV-1 RT inhibitor and their antifungal activity. Bioorg Chem 2016; 64: 66-73.
[http://dx.doi.org/10.1016/j.bioorg.2015.12.005] [PMID: 26717022]
[31]
Franzblau SG, DeGroote MA, Cho SH, et al. Comprehensive analysis of methods used for the evaluation of compounds against Mycobac-terium tuberculosis. Tuberculosis (Edinb) 2012; 92(6): 453-88.
[http://dx.doi.org/10.1016/j.tube.2012.07.003] [PMID: 22940006]
[32]
Cho SH, Warit S, Wan B, et al. Low-oxygen-recovery assay for high-throughput screening of compounds against non-replicating Myco-bacterium tuberculosis. Antimicrob Agents Chemother 2007; 51(4): 1380-5.
[http://dx.doi.org/10.1128/AAC.00055-06] [PMID: 17210775]
[33]
Penta A, Franzblau S, Wan B, Murugesan S. Design, synthesis and evaluation of diarylpiperazine derivatives as potent anti-tubercular agents. Eur J Med Chem 2015; 105: 238-44.
[http://dx.doi.org/10.1016/j.ejmech.2015.10.024] [PMID: 26498570]
[34]
Zhou B, Shetye G, Yu Y, et al. Antimycobacterial rufomycin analogues from Streptomyces atratus Strain MJM3502. J Nat Prod 2020; 83(3): 657-67.
[http://dx.doi.org/10.1021/acs.jnatprod.9b01095] [PMID: 32031795]
[35]
Dallakyan S, Olson AJ. Small-Molecule Library Screening by Docking with PyRx Chemical biology methods in molecular biology. New York, NY: Humana Press 2014; Vol. 1263: pp. 243-50.
[http://dx.doi.org/10.1007/978-1-4939-2269-7_19]
[36]
Guex N, Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis 1997; 18(15): 2714-23.
[http://dx.doi.org/10.1002/elps.1150181505] [PMID: 9504803]
[37]
Lipinski CA. Lead- and drug-like compounds: The rule-of-five revolution. Drug Discov Today Technol 2004; 1(4): 337-41.
[http://dx.doi.org/10.1016/j.ddtec.2004.11.007] [PMID: 24981612]
[38]
Leeson PD, Springthorpe B. The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov 2007; 6(11): 881-90.
[http://dx.doi.org/10.1038/nrd2445] [PMID: 17971784]
[39]
Pires DEV, Blundell TL, Ascher DB. pkCSM: Predicting small-molecule pharmacokinetic and toxicity properties using graph-based signa-tures. J Med Chem 2015; 58(9): 4066-72.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00104] [PMID: 25860834]

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