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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

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Research Article

Synthesis and In-silico Identification of New Bioactive 1,3,4-oxadiazole Tagged 2,3-dihydroimidazo[1,2-a]pyridine Derivatives

Author(s): Bhagwat S. Jadhav, Vipul P. Purohit, Ramesh S. Yamgar*, Rajesh S. Kenny, Suraj N. Mali, Hemchandra K. Chaudhari and Mustapha C. Mandewale

Volume 17, Issue 4, 2021

Published on: 25 June, 2020

Page: [318 - 330] Pages: 13

DOI: 10.2174/1573407216999200625222014

Price: $65

Abstract

Background: Tuberculosis (TB) continues to be the most threatening cause of death in recent years. There is an urgent need to search more potent, less toxic antitubercular agents.

Methods: A set of five new 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) was synthesized and screened in-vitro for their antibacterial activity against Mycobacterium tuberculosis (H37 RV strain) ATCC No-27294.

Results: Compound 4b displayed potent antitubercular activity at MIC 6.25 μg/mL. In-silico molecular docking studies were performed for the evaluation of the binding patterns of compounds 4a-4e in the binding site of proteins like, Pantothenate synthatase and enoyl acyl reductase inhibitor. The outcomes of the in-vitro antitubercular studies were in good agreement with the molecular docking studies. These newly synthesized compounds were found to have a good ADMET profile. We also explored possible anticancer activity using in-silico methods.

Conclusion: These results show that readily synthesized 1,3,4-oxadiazolyl-imidazo-1,2-pyridine derivatives (4a-4e) are attracting a new class of potent anti-TB targets as well as possible anticancer activity that worth additional opportunities for improvements.

Keywords: Oxadiazole, imidazole, tuberculosis, anticancer, molecular docking, zibotentan.

Graphical Abstract

[1]
Global tuberculosis report 2018. Geneva: World Health Organization, ISBN 978-92-4-156564-6.2018. Licence: CC BY-NC-SA 3.0 IGO.
[2]
Thakare, R.; Soni, I.; Dasgupta, A.; Chopra, S. Delamanid for the treatment of pulmonary multidrug-resistant tuberculosis. Drugs Today (Barc), 2015, 51(2), 117-123.
[http://dx.doi.org/10.1358/dot.2015.51.2.2245645] [PMID: 25756067]
[3]
"WHO Model List of Essential Medicines (19th List)". World Health Organization., 2015.
[4]
Blair, H.A.; Scott, L.J. Delamanid: A review of its use in patients with multidrug-resistant tuberculosis. Drugs, 2015, 75(1), 91-100.
[http://dx.doi.org/10.1007/s40265-014-0331-4] [PMID: 25404020]
[5]
Singh, R.; Manjunatha, U.; Boshoff, H.I.; Ha, Y.H.; Niyomrattanakit, P.; Ledwidge, R.; Dowd, C.S.; Lee, I.Y.; Kim, P.; Zhang, L.; Kang, S.; Keller, T.H.; Jiricek, J.; Barry, C.E.P.A., III PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science, 2008, 322(5906), 1392-1395.
[http://dx.doi.org/10.1126/science.1164571] [PMID: 19039139]
[6]
Hemant, N.; Raundal, R.P.; Jadhav, A.A. Patil; Bobade, V. D. Synthesis and antimicrobial studies of 2-(5-substituted)-1, 3, 4-oxadiazole-2-yl)-H-imidazo [1, 2, α] pyridine derivatives. J. Chem. Pharm. Res., 2014, 6(7), 102-108.
[7]
Fusun, G.; Nesrin, C.; Dilek, S.; Meltem, U.T. Synthesis of novel imidazo[1,2-a]pyridines and evaluation of their antifungal activities. J. Chem., 2014, 38(4), 581-591.
[8]
Junichi, K.; Mitsuaki, M.; Futoshi, M.; Yoshiaki, O.; Yoshinori, S.; Hidenori, S.; Daiya, S.; Manabu, S.; Shuichi, S.; Yasutaka, T.; Hiromitsu, Y.; Naoki, Y. Nitrogenous fused-ring compound having pyrazolyl group as substituent and medicinal composition thereof. EP1382603A4, 2002.
[9]
Shelke, S.; Salunkhe, N.; Sangale, S.; Bhalerao, S.; Naik, N.; Mhaske, G.; Jadhav, R.; Karale, B. Synthesis and antimicrobial screening of some fluorinated azoles containing (2-(6-Methyl-2-P-tolyl-lH-imidazo[1,2-a]pyridin-3-yl) nucleus J. Korean Chem. Soc., 2010, 54(1), 59-64.
[http://dx.doi.org/10.5012/jkcs.2010.54.01.059]
[10]
Hu, X.; Wan, B.; Liu, Y.; Shen, J.; Franzblau, S.G.; Zhang, T.; Ding, K.; Lu, X. Identification of pyrazolo[1,5-a]pyridine-3-carboxamide diaryl derivatives as drug resistant antituberculosis agents. ACS Med. Chem. Lett., 2019, 10(3), 295-299.
[http://dx.doi.org/10.1021/acsmedchemlett.8b00410] [PMID: 30891129]
[11]
James, N.D.; Growcott, J.W. Zibotentan. Drugs Future, 2009, 34(8), 624-633.
[12]
Jones, A.M.; Helm, J.M. Emerging treatments in cystic fibrosis. Drugs, 2009, 69(14), 1903-1910.
[http://dx.doi.org/10.2165/11318500-000000000-00000] [PMID: 19747007]
[13]
Summa, V.; Petrocchi, A.; Bonelli, F.; Crescenzi, B.; Donghi, M.; Ferrara, M.; Fiore, F.; Gardelli, C.; Gonzalez Paz, O.; Hazuda, D.J.; Jones, P.; Kinzel, O.; Laufer, R.; Monteagudo, E.; Muraglia, E.; Nizi, E.; Orvieto, F.; Pace, P.; Pescatore, G.; Scarpelli, R.; Stillmock, K.; Witmer, M.V.; Rowley, M. Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J. Med. Chem., 2008, 51(18), 5843-5855.
[http://dx.doi.org/10.1021/jm800245z] [PMID: 18763751]
[14]
Husain, A.; Ajmal, M. Synthesis of novel 1,3,4-oxadiazole derivatives and their biological properties. Acta Pharm., 2009, 59(2), 223-233.
[http://dx.doi.org/10.2478/v10007-009-0011-1] [PMID: 19564146]
[15]
Deshmukh, A.A.; Sattur, P.B.; Sheth, U.K. Synthesis and pharmacology of 2, 3-diphenylpropionhydrazides and hydrazones. Indian J. Exp. Biol., 1976, 14(2), 166-168.
[PMID: 992732]
[16]
Kidwai, M.; Negi, N.; Chowdhury, S.R. Novel 1,2,4-triazole, 1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives and their pharmacological screening. Acta Pharm., 1995, 45(4), 511-516.
[17]
Bala, S.; Saini, V.; Kamboj, S.; Prasad, D.N. Review exploring antiflammatory potential of 1,2,4-Oxadiazole derivative as promomising lead. Int. J. Pharm. Sci. Rev. Res., 2012, 17, 84-89.
[18]
Omar, F.; Mahfouz, N.; Rahman, M. Design, synthesis and antiinflammatory activity of some 1,3,4-oxadiazole derivatives. Eur. J. Med. Chem., 1996, 31(10), 819-825.
[http://dx.doi.org/10.1016/0223-5234(96)83976-6] [PMID: 22026938]
[19]
Moth, C.W.; Prusakiewicz, J.J.; Marnett, L.J.; Lybrand, T.P. Stereoselective binding of indomethacin ethanolamide derivatives to cyclooxygenase-1. J. Med. Chem., 2005, 48(10), 3613-3620.
[http://dx.doi.org/10.1021/jm0494164] [PMID: 15887968]
[20]
Kinjal, D.P.; Prajapati, S.M.; Panchal, S.N.; Patel, H.D. Review of Synthesis of 1,3,4-Oxadiazole Derivatives. Syn. Com., 2014, 44(13), 1859-1875.
[http://dx.doi.org/10.1080/00397911.2013.879901]
[21]
Amir, M.; Agarwal, R. Synthesis and anti-inflammatory activity of 5-(8- quinilinoxymethyl)-1, 3, 4-oxadiazoles, 1, 3, 4-thiadiazoles and 1, 2, 4 triazoles. Indian J. Het. Chem, 1998, 7(3), 225-228.
[22]
Tsitsa, P.; Papadaki-Valiraki, A.; Siatra-Papastaikoudi, T.; Papadopoulou-Daifoiti, Z.; Vamvakidis, A. Synthesis and anticonvulsive activity of some new bisubstituted 1,3,4-oxadiazoles and 1H-1,2,4-triazoles. Ann. Pharm. Fr., 1989, 47(5), 296-303.
[PMID: 2637649]
[23]
Huguet, G. J.; Fauran, C. P.; Douzon, C. A.; Raynaud, M.; Thomas Janine, M. Derivatives of 2-hydroxymethyl-1,3,4-oxadiazole US Patent 3912747 (A), 1975.
[24]
Zarghi, A.; Faizi, M.; Shafaghi, B.; Ahadian, A.; Khojastehpoor, H.R.; Zanganeh, V.; Tabatabai, S.A.; Shafiee, A. Design and synthesis of new 2-substituted-5-(2-benzylthiophenyl)-1,3,4-oxadiazoles as benzodiazepine receptor agonists. Bioorg. Med. Chem. Lett., 2005, 15(12), 3126-3129.
[http://dx.doi.org/10.1016/j.bmcl.2005.04.018] [PMID: 15876530]
[25]
Hutt, M.P.; Elslager, E.F.; Werbel, L.M. 2-Phenyl-5-(trichloromethyl)-1,3,4-oxadiazoles, A new class of antimalarial substances. J. Heterocycl. Chem., 1970, 7(3), 511-518.
[http://dx.doi.org/10.1002/jhet.5570070308]
[26]
Mogilaiah, K.; Babu, H.R.; Rao, R.B. Synthesis and antimicrobial activity of some new 1,3,4-oxadiazolyl-1,8-naphthyridines. Indian J. Heterocycl. Chem., 2000, 10(2), 109-112.
[27]
Shehata, I.A.; Nasr, M.N.; El-Subbagh, H.I.; Gineinah, M.M.; Kheira, S.M. Synthesis and biological testing of certain 1, 3, 4-oxadiazole and 1, 2, 4-triazole derivatives as potential antimicrobial agents. Sci. Pharm., 1996, 64(2), 133-143.
[28]
Gaonkar, S.L.; Rai, K.M.L.; Prabhuswamy, B. Synthesis and antimicrobial studies of a new series of 2-[4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl]-5-substituted-1,3,4-oxadiazoles. Eur. J. Med. Chem., 2006, 41(7), 841-846.
[http://dx.doi.org/10.1016/j.ejmech.2006.03.002] [PMID: 16616395]
[29]
Saxena, S.; Verma, M.; Saxena, A.K.; Shanker, K. 1,3,4-oxidiazole thiones as inflammation inhibitors. Indian J. Pharm. Sci., 1992, 54(1), 1-3.
[30]
Cesur, N.; Birteksoz, S.; Otuk, G. Synthesis and biological evaluation of some new thiosemicarbazide, 4-thiazolidinone, 1,3,4-oxadiazole and 1,2,4-triazole-3-thione derivatives bearing imidazo[1,2-a]pyridine moiety. Acta Pharm. Turcica, 2002, 44(1), 23-41.
[31]
Xu, W.M.; Han, F.F.; He, M.; Hu, D.Y.; He, J.; Yang, S.; Song, B.A. Inhibition of tobacco bacterial wilt with sulfone derivatives containing an 1,3,4-oxadiazole moiety. J. Agric. Food Chem., 2012, 60(4), 1036-1041.
[http://dx.doi.org/10.1021/jf203772d] [PMID: 22208183]
[32]
Rafal, F. Biological activities of the compounds bearing 1,3,4-Oxa(thia)diazole ring. Asian J. Chem., 2005, 17(4), 2063-2075.
[33]
Ateş, O.; Kocabalkanli, A.; Saniş, G.O.; Ekinci, A.C.; Vidin, A. Synthesis and antibacterial activity of 5-aryl-2-[(alpha-chloro-alpha-phenylacetyl/alpha-bromopropionyl)amino]- 1,3,4-oxadiazoles and 2-[(5-aryl-1,3,4-oxadiazol-2-yl)imino]-5-phenyl/methyl-4-thiazolidinone s. Arzneimittelforschung, 1997, 47(10), 1134-1138.
[PMID: 9368708]
[34]
Holla, B.S.; Gonsalves, R.; Shenoy, S. Synthesis and antibacterial studies of a new series of 1,2-bis(1,3, 4-oxadiazol-2-yl)ethanes and 1,2-bis(4-amino-1,2, 4-triazol-3-yl)ethanes. Eur. J. Med. Chem., 2000, 35(2), 267-271.
[http://dx.doi.org/10.1016/S0223-5234(00)00154-9] [PMID: 10758288]
[35]
Laddi, U.V.; Desai, S.R.; Bennur, R.S.; Bennur, S.C. Some new 1, 3, 4-oxadiazoles as antimicrobial agents. Indian J. Heterocycl. Chem., 2002, 11(4), 319-322.
[36]
Padmavathi, V.; Sudhakar Reddy, G.; Padmaja, A.; Kondaiah, P.; Ali-Shazia, Synthesis, antimicrobial and cytotoxic activities of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles. Eur. J. Med. Chem., 2009, 44(5), 2106-2112.
[http://dx.doi.org/10.1016/j.ejmech.2008.10.012] [PMID: 19036476]
[37]
Kumar, D.; Sundaree, S.; Johnson, E.O.; Shah, K.; Kumar, D.; Sundaree, S.; Johnson, E.O.; Shah, K. An efficient synthesis and biological study of novel indolyl-1,3,4-oxadiazoles as potent anticancer agents. Bioorg. Med. Chem. Lett., 2009, 19(15), 4492-4494.
[http://dx.doi.org/10.1016/j.bmcl.2009.03.172] [PMID: 19559607]
[38]
Musser, J.H.; Brown, R.E.; Loev, B.; Bailey, K.; Jones, H.; Kahen, R.; Huang, F.C.; Khandwala, A.; Leibowitz, M.; Sonnino-Goldman, P. Synthesis of 2-(2,3-dihydro-2-oxo-1,3,4-oxadiazol-5-yl) benzo heterocycles. A novel series of orally active antiallergic agents. J. Med. Chem., 1984, 27(2), 121-125.
[http://dx.doi.org/10.1021/jm00368a004] [PMID: 6198518]
[39]
Shirote, P.J.; Bhatia, M.S. Synthesis, characterization and anti-inflammatory activity of 5-[((5-Substituted-aryl)-1,3,4-thiadiazol-2-yl)thio]-n-alkyl-1,3,4-oxadiazole-2-thiol. Chin. J. Chem., 2010, 28(8), 1429-1436.
[http://dx.doi.org/10.1002/cjoc.201090244]
[40]
Zou, X.J.; Lai, L.H.; Jin, G.Y.; Zhang, Z.X. Synthesis, fungicidal activity, and 3D-QSAR of pyridazinone-substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles. J. Agric. Food Chem., 2002, 50(13), 3757-3760.
[http://dx.doi.org/10.1021/jf0201677] [PMID: 12059155]
[41]
Abate, G.; Mshana, R.N.; Miörner, H. Evaluation of a colorimetric assay based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) for rapid detection of rifampicin resistance in Mycobacterium tuberculosis. Int. J. Tuberc. Lung Dis., 1998, 2(12), 1011-1016.
[PMID: 9869118]
[42]
Mali, S.N.; Chaudhari, H.K. Computational studies on imidazo [1,2-a] pyridine-3-carboxamide analogues as antimycobacterial agents: Common pharmacophore generation, atom-based 3D-QSAR, molecular dynamics simulation, QikProp, molecular docking and prime MMGBSA approaches. Open Pharm. Sci. J., 2018, 5(1), 12-23.
[http://dx.doi.org/10.2174/1874844901805010012]
[43]
Mali, S.N.; Chaudhari, H.K. Molecular modelling studies on adamantane-based Ebola virus GP-1 inhibitors using docking, pharmacophore and 3D-QSAR. SAR QSAR Environ. Res., 2019, 30(3), 161-180.
[http://dx.doi.org/10.1080/1062936X.2019.1573377] [PMID: 30786763]
[44]
Mali, S.N.; Sawant, S.; Chaudhari, H.K.; Mandewale, M.C. In silico appraisal, Synthesis, Antibacterial screening and DNA cleavage for 1,2,5-thiadiazole derivative. Curr Comput Aided Drug Des, 2019, 15(5), 445-455.
[http://dx.doi.org/10.2174/1573409915666190206142756] [PMID: 30727910]
[45]
Mishra, V.R.; Ghanavatkar, C.W.; Mali, S.N.; Qureshi, S.I.; Chaudhari, H.K.; Sekar, N. Design, synthesis, antimicrobial activity and computational studies of novel azo linked substituted benzimidazole, benzoxazole and benzothiazole derivatives. Comput. Biol. Chem., 2019, 78, 330-337.
[http://dx.doi.org/10.1016/j.compbiolchem.2019.01.003] [PMID: 30639681]
[46]
Jadhav, B.S.; Yamgar, R.S.; Kenny, R.S.; Mali, S.N.; Chaudhari, H.K.; Mandewale, M.C. Synthesis, in-silico and biological studies of thiazolyl-2h-chromen-2-one derivatives as potent antitubercular agents. Curr. Comput. Aided Drug Des., 2020, 16(5), 511-522.
[http://dx.doi.org/10.2174/1386207322666190722162100]
[47]
Mishra, V.R.; Ghanavatkar, C.W.; Mali, S.N.; Chaudhari, H.K.; Sekar, N. Schiff base clubbed benzothiazole: synthesis, potent antimicrobial and MCF-7 anticancer activity, DNA cleavage and computational study. J. Biomol. Struct. Dyn., 2019, 1-14.
[http://dx.doi.org/10.1080/07391102.2019.1621213] [PMID: 31107179]
[48]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7, 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[49]
Mollica, A.; Stefanucci, A.; Feliciani, F.; Lucente, G.; Pinnen, F. Synthesis of (S)-5, 6-dibromo-tryptophan derivatives as building blocks for peptide chemistry. Tetrahedron Lett., 2011, 52(20), 2583-2585.
[http://dx.doi.org/10.1016/j.tetlet.2011.03.041]
[50]
Stefanucci, A.; Angeli, A.; Dimmito, M.P.; Luisi, G.; Del Prete, S.; Capasso, C.; Donald, W.A.; Mollica, A.; Supuran, C.T. Activation of β- and γ-carbonic anhydrases from pathogenic bacteria with tripeptides. J. Enzyme Inhib. Med. Chem., 2018, 33(1), 945-950.
[http://dx.doi.org/10.1080/14756366.2018.1468530] [PMID: 29747543]
[51]
Mollica, A.; Zengin, G.; Durdagi, S.; Ekhteiari Salmas, R.; Macedonio, G.; Stefanucci, A.; Dimmito, M.P.; Novellino, E. Combinatorial peptide library screening for discovery of diverse α-glucosidase inhibitors using molecular dynamics simulations and binary QSAR models. J. Biomol. Struct. Dyn., 2019, 37(3), 726-740.
[http://dx.doi.org/10.1080/07391102.2018.1439403] [PMID: 29421954]
[52]
Patel, M.H.; Patel, D.K.; Patel, D.H. Facile synthesis and biological evaluation of New Mannich products as potential antibacterial, antifungal and antituberculosis agents: Molecular docking study. Curr. Bioact. Compd., 2017, 13(1), 47-58.
[http://dx.doi.org/10.2174/1573407212666160517145130]
[53]
Primm, T.P.; Franzblau, S.G. Recent advances in methodologies for the discovery of antimycobacterial drugs. Curr. Bioact. Compd., 2007, 3(3), 201-208.
[http://dx.doi.org/10.2174/157340707781695550]
[54]
Guillemont, J.; Lieby-Muller, F.; Lounis, N.; Balemans, W.; Koul, A.; Andries, K. New anti-tuberculosis drugs in clinical development: an overview. Curr. Bioact. Compd., 2009, 5(2), 137-154.
[http://dx.doi.org/10.2174/157340709788451975]
[55]
Palumbo Piccionello, A.; Guarcello, A. Bioactive compounds containing benzoxadiazole, benzothiadiazole, benzotriazole. Curr. Bioact. Compd., 2010, 6(4), 266-283.
[http://dx.doi.org/10.2174/157340710793237308]
[56]
Thakral, S.; Singh, V. Recent development on importance of heterocyclic amides as potential bioactive molecules: A review. Curr. Bioact. Compd., 2019, 15(3), 316-336.
[http://dx.doi.org/10.2174/1573407214666180614121140]
[57]
Chabukswar, V.; Pawar, D.; Handore, K.; Shisodia, S.; Diwate, B.; Adhav, P.; Jagdale, S.; Chabukswar, A.; Gaikwad, V.; Dallavalle, S. Biopolymer catalysed synthesis of 6-methyl-4-phenylcarbamoyl-1, 2, 3, 4-tetrahydropyrimidine-2-ones and evaluation of their anti-bacterial and anti-tubercular activities. Curr. Bioact. Compd., 2019, 15(4), 408-414.
[http://dx.doi.org/10.2174/1573407214666180503114844]
[58]
Naikoo, A. R.; A Mir, M.; Bhat, S.; Tomar, R.; A Bhat, R.; A Malla, M. Biological activities and synthetic approaches of dihydropyrimidinones and thiones-an updated review. Curr. Bioact. Compd., 2016, 12(4), 236-250.
[http://dx.doi.org/10.2174/1573407212666160517150045]
[59]
Talwan, P.; Chaudhary, S.; Kumar, K.K.; Rawal, R. Chemical and medicinal versatility of substituted 1, 4-dihydropyridines. Curr. Bioact. Compd., 2017, 13(2), 109-120.
[http://dx.doi.org/10.2174/1573407212666160607090202]
[60]
Chaudhari, H.A.; Siddikia, A.D.; Manohara, Y. Design and synthesis of novel oxadiazole and diphenyl ether hydrazone derivatives of coumarin as potential antibacterial agents. Curr. Bioact. Compd., 2017, 13(4), 318-325.
[http://dx.doi.org/10.2174/1573407213666161128121435]

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