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Anti-Infective Agents

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ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

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Research Article

Synthesis and Biological Activity of 3-(substitutedphenyl)-6-(4-methoxy phenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine: Part II

Author(s): Niranjan Kaushik*, Nitin Kumar, Anoop Kumar and Vikas Sharma

Volume 19, Issue 2, 2021

Published on: 17 June, 2020

Page: [162 - 168] Pages: 7

DOI: 10.2174/2211352518666200617144227

Price: $65

Abstract

Background: Fungal infections are opportunistic infections that become a serious problem for human health.

Objective: Considering the antifungal potential of the triazole nucleus, the study was carried out with the objective of synthesizing some novel triazole derivatives with antifungal potential.

Methods: 1,2,4-triazole derivatives were synthesized via a two-step reaction (reported earlier). The first step involves the reaction of substituted benzoic acid with thiocarbohydrazide to form 4- amino-3-(substituted phenyl)-5-mercapto-1, 2, 4-triazole derivatives (1a-1k) while in the second step, synthesized compounds (1a-1k) were then subsequently treated with substituted acetophenone to yield substituted (4-methoxyphenyl-7H-[1, 2, 4] triazolo [3, 4-b][1,3,4] thiadiazine derivatives (2a-2k). All synthesized compounds were characterized by IR, 1H NMR, and Mass spectral data analysis and were screened for their antifungal properties against different fungal strains i.e. Candida tropicalis (ATCC-13803, ATCC-20913), Candida albicans (ATCC-60193), Candida inconspicua (ATCC-16783) and Candida glabrata (ATCC-90030, ATCC-2001).

Results: Compound 2d displayed better percentage inhibition (26.29%, 24.81%) than fluconazole (24.44%, 22.96%) against ATCC-16783, ATCC-2001 fungal strains respectively at 100μg/ml. Compound 2f also displayed better percentage inhibition (28.51%) against ATCC-90030 as compared to fluconazone (27.4%) at 200 μg/ml. Similarly, compounds 2e and 2j also exhibited better antifungal properties than fluconazole at 200μg/ml. Compound 2e was found most potent against ATCC-13803 (30.37%) and ATCC-90030 (30.37%) fungal strains as compared to fluconazole (28.14%, 27.4%) at 200 μg/ml respectively whereas compound 2j exhibited better antifungal activity (28.51%) against ATCC-60193 than fluconazole (27.7%) at 200 μg/ml.

Conclusion: The results were in accordance with our assertions for triazole derivatives, as all compounds displayed moderate to good antifungal activity.

Keywords: Triazole, thiadiazine, fluconazole, thiocarbohydrazide, benzoic acid, antifungal activity.

Graphical Abstract

[1]
Kanafani, Z.A.; Perfect, J.R. Antimicrobial resistance: resistance to antifungal agents: mechanisms and clinical impact. Clin. Infect. Dis., 2008, 46(1), 120-128.
[http://dx.doi.org/10.1086/524071] [PMID: 18171227]
[2]
Boateng, C.A.; Eyunni, S.V.; Zhu, X.Y.; Etukala, J.R.; Bricker, B.A.; Ashfaq, M.K.; Jacob, M.R.; Khan, S.I.; Walker, L.A.; Ablordeppey, S.Y. Benzothieno[3,2-b]quinolinium and 3-(phenylthio)quinolinium compounds: Synthesis and evaluation against opportunistic fungal pathogens. Bioorg. Med. Chem., 2011, 19(1), 458-470.
[http://dx.doi.org/10.1016/j.bmc.2010.11.008] [PMID: 21134759]
[3]
Senel, P.; Tichotová, L.; Votruba, I.; Buchta, V.; Spulák, M.; Kunes, J.; Nobilis, M.; Krenk, O.; Pour, M. Antifungal 3,5-disubstituted furanones: From 5-acyloxymethyl to 5-alkylidene derivatives. Bioorg. Med. Chem., 2010, 18(5), 1988-2000.
[http://dx.doi.org/10.1016/j.bmc.2010.01.030] [PMID: 20153653]
[4]
Deepa, A.; Nair, B.J.; Sivakumar, T.; Joseph, A.P. Uncommon opportunistic fungal infections of oral cavity: A review. J. Oral Maxillofac. Pathol., 2014, 18(2), 235-243.
[http://dx.doi.org/10.4103/0973-029X.140765] [PMID: 25328305]
[5]
Gadhave, P.P.; Dighe, N.S.; Pattan, S.R.; Deotarse, P.; Musmade, D.S.; Shete, R. Current biological and synthetic profile of triazoles: A review. Ann. Biol. Res., 2010, 1, 82-89.
[6]
Shalini, K.; Kumar, N.; Drabu, S.; Sharma, P.K. Advances in synthetic approach to and antifungal activity of triazoles. Beilstein J. Org. Chem., 2011, 7, 668-677.
[http://dx.doi.org/10.3762/bjoc.7.79] [PMID: 21804864]
[7]
Tozkoparan, B.; Gökhan, N.; Aktay, G.; Yeşilada, E.; Ertan, M. 6-Benzylidenethiazolo[3,2-b]-1,2,4-triazole-5(6H)-ones substituted withibuprofen: synthesis, characterization and evaluation of anti-inflammatory activity. Eur. J. Med. Chem., 2000, 35(7-8), 743-750.
[http://dx.doi.org/10.1016/S0223-5234(00)00157-4] [PMID: 10960191]
[8]
Mathew, V.; Keshavayya, J.; Vaidya, V.P.; Giles, D. Studies on synthesis and pharmacological activities of 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and their dihydro analogues. Eur. J. Med. Chem., 2007, 42(6), 823-840.
[http://dx.doi.org/10.1016/j.ejmech.2006.12.010] [PMID: 17331622]
[9]
Kaplancikli, Z.A.; Turan-Zitouni, G.; Ozdemir, A.; Revial, G. New triazole and triazolothiadiazine derivatives as possible antimicrobial agents. Eur. J. Med. Chem., 2008, 43(1), 155-159.
[http://dx.doi.org/10.1016/j.ejmech.2007.03.019] [PMID: 17499887]
[10]
Mithun, A.; Holla, B.S. Convenient synthesis of some triazolothiadiazoles and triazolothiadiazines carrying 4-methylthiobenzyl moiety as possible antimicrobial agents. J. Pharm. Toxicol., 2007, 4, 256-263.
[11]
Shivarama Holla, B.; Sooryanarayana Rao, B.; Sarojini, B.K.; Akberali, P.M.; Suchetha Kumari, N. Synthesis and studies on some new fluorine containing triazolothiadiazines as possible antibacterial, antifungal and anticancer agents. Eur. J. Med. Chem., 2006, 41(5), 657-663.
[http://dx.doi.org/10.1016/j.ejmech.2006.02.001] [PMID: 16616396]
[12]
Holla, B.S.; Akberali, P.M.; Shivananda, M.K. Studies on nitrophenylfuran derivatives part Xii. synthesis, characterization, antibacterial and antiviral activities of some nitrophenylfurfurylidene-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines. Farmaco, 2001, 56(12), 919-927.
[http://dx.doi.org/10.1016/S0014-827X(01)01124-7] [PMID: 11829111]
[13]
el-Khawass, S.M.; Khalil, M.A.; Hazzaa, A.A.; Bassiouny, H.A.; Loutfy, N.F. Synthesis of some 1,2,4-triazolo [3,4-b] [1,3,4]thiadiazoles as potential anthelmintics. Farmaco, 1989, 44(7-8), 703-709.
[PMID: 2590368]
[14]
Al-Masoudi, N.A.; Al-Soud, Y.A. New sulphonamide and carboxamide derivatives of acyclic C-nucleosides of triazolo-thiadiazole and the thiadiazine analogues. Synthesis, anti-HIV, and antitumor activities. Part 2. Nucleosides Nucleotides Nucleic Acids, 2008, 27(9), 1034-1044.
[http://dx.doi.org/10.1080/15257770802271771] [PMID: 18711666]
[15]
Kamel, M.M.; Megally Abdo, N.Y. Synthesis of novel 1,2,4-triazoles, triazolothiadiazines and triazolothiadiazoles as potential anticancer agents. Eur. J. Med. Chem., 2014, 86, 75-80.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.047] [PMID: 25147148]
[16]
Al-Soud, Y.A.; Al-Masoudi, N.A.; Loddo, R.; La Colla, P. In-vitro anti-HIV and antitumor activity of new 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and thiadiazine analogues. Arch. Pharm. (Weinheim), 2008, 341(6), 365-369.
[http://dx.doi.org/10.1002/ardp.200700272] [PMID: 18493972]
[17]
Aytaç, S.P.; Tozkoparan, B.; Kaynak, F.B.; Aktay, G.; Göktaş, O.; Unüvar, S. Synthesis of 3,6-disubstituted 7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines as novel analgesic/anti-inflammatory compounds. Eur. J. Med. Chem., 2009, 44(11), 4528-4538.
[http://dx.doi.org/10.1016/j.ejmech.2009.06.026] [PMID: 19632747]
[18]
Hussein, M.A.; Shaker, R.M.; Ameen, M.A.; Mohammed, M.F. Synthesis, anti-inflammatory, analgesic, and antibacterial activities of some triazole, triazolothiadiazole, and triazolothiadiazine derivatives. Arch. Pharm. Res., 2011, 34(8), 1239-1250.
[http://dx.doi.org/10.1007/s12272-011-0802-z] [PMID: 21910044]
[19]
Mir, I.; Siddiqui, M.T.; Comrie, A. Antituberculosis agents. I. Alpha-(5-(2-Furyl)-1,2,4-triazol-3-ylthio) acethydrazide and related compounds. Tetrahedron, 1970, 26(22), 5235-5238.
[http://dx.doi.org/10.1016/S0040-4020(01)98732-0] [PMID: 5499898]
[20]
Li, Z.; Bai, X.; Deng, Q.; Zhang, G.; Zhou, L.; Liu, Y.; Wang, J.; Wang, Y. Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains. Bioorg. Med. Chem., 2017, 25(1), 213-220.
[http://dx.doi.org/10.1016/j.bmc.2016.10.027] [PMID: 27810439]
[21]
Hester, J.B.; Ludens, J.H.; Emmert, D.E.; West, B.E. 1-(2-aminoethyl)-6-aryl-4H- [1,2,4]triazolo[4,3-a][1,4]benzodiazepines with diuretic and natriuretic activity. J. Med. Chem., 1989, 32(6), 1157-1163.
[http://dx.doi.org/10.1021/jm00126a003] [PMID: 2724291]
[22]
Sahu, J.K.; Ganguly, S.; Yasir, M. Synthesis, SAR and molecular docking studies of certain New derivatives of 1,2,4-triazolo [3,4-b][1,3,4] thiadiazole as potent antimicrobial agents. Antiinfect. Agents, 2018, 16, 40-48.
[http://dx.doi.org/10.2174/2211352516666180209125045]
[23]
Shingare, R.M.; Patil, Y.S.; Sangshetti, J.N.; Damale, M.G.; Rajani, D.P.; Madje, B.R. Synthesis, antimicrobial evaluation and docking study of some pyrazole bearing [1, 2,4]triazolo[3, 4-b][1, 3,4] thiadiazole derivatives. ChemistrySelect, 2018, 3, 3899-3903.
[http://dx.doi.org/10.1002/slct.201800373]
[24]
Demirayak, S.; Kayagil, I.; Yurttas, L.; Er, S. Synthesis and antifungal activity evaluation of new 1, 2, 4-triazole derivatives bearing salicylidene hydrazide moiety. Lett. Drug Des. Discov., 2016, 13(2), 178-184.
[http://dx.doi.org/10.2174/1570180812666150723001545]
[25]
Yang, L.; Bao, X.P. Synthesis of novel 1, 2, 4-triazole derivatives containing the quinazolinylpiperidinyl moiety and N-(substituted phenyl) acetamide group as efficient bactericides against the phytopathogenic bacterium Xanthomonas oryzae pv. oryzae. RSC adv, 2017, 7(54), 34005-34011.
[26]
Ezelarab, H.A.; Hassan, H.A.; Abbas, S.H.; El-Baky, A.; Rehab, M.; Aburahama, G.A. Design, synthesis and antifungal activity of 1, 2, 4-triazole/or 1, 3, 4-oxadiazole-ciprofloxacin hybrids. J. Adv. Biomed. Pharm. Sci., 2018, 1(2), 78-84.
[http://dx.doi.org/10.21608/jabps.2018.3774.1013]
[27]
Kaushik, N.; Kumar, N.; Kumar, A. Synthesis and biological activity of 3-(substitutedphenyl)-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine. Immun. Endoc. Metab. Agents in Med. Chem, 2016, 16(1), 70-80.
[28]
Patel, R.B.; Desai, P.S.; Desai, K.R.; Chikhalia, K.H. Synthesis of pyrimidine based thiazolidinones and azetidinones: Antimicrobial and antitubercular agents. Indian J. Chem., 2006, 45, 773-778.
[http://dx.doi.org/10.1002/chin.200628143]
[29]
Ballell, L.; Field, R.A.; Chung, G.A.; Young, R.J. New thiopyrazolo[3,4-d]pyrimidine derivatives as anti-mycobacterial agents. Bioorg. Med. Chem. Lett., 2007, 17(6), 1736-1740.
[http://dx.doi.org/10.1016/j.bmcl.2006.12.066] [PMID: 17239593]

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