European Journal of Chemistry

Synthesis, Type II diabetes inhibitory activity, antimicrobial evaluation, and docking studies of N'-arylidene-2-((7-methylbenzo[4,5]thiazolo[2,3-c] [1,2,4]triazol-3-yl)thio)acetohydrazides

Article Sidebar

PDF
Published: Dec 31, 2022
DOI: https://doi.org/10.5155/eurjchem.13.4.426-434.2315
Keywords:
α-Amylase, Hydrazones, Benzothiazole, Docking studies, Acetohydrazide, Antimicrobial activity
Section
Research Article
Issue
Vol. 13 No. 4 (2022): December 2022
Dates
Received 2022-07-25
Accepted 2022-09-09
Published 2022-12-31
Crossmark


Main Article Content

Satbir Mor
Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar-125001, Haryana, India
https://orcid.org/0000-0003-2114-0611
Suchita Sindhu
Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar-125001, Haryana, India
https://orcid.org/0000-0002-3447-0831
Mohini Khatri
Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar-125001, Haryana, India
https://orcid.org/0000-0002-8283-7167
Ravinder Punia
Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar-125001, Haryana, India
https://orcid.org/0000-0001-5085-3376
Komal Jakhar
Department of Chemistry, Maharishi Dayanand University, Rohtak-124001, Haryana, India
https://orcid.org/0000-0003-3063-0655

Abstract

N'-Arylidene-2-((7-methylbenzo[4, 5]thiazolo[2,3-c][1, 2, 4]triazol-3-yl)thio)acetohydrazides (6a-j) were prepared by condensation of 2-((7-methylbenzo[4,5]thiazolo[2,3-c][1,2,4] triazol-3-yl)thio)acetohydrazide with appropriately substituted benzaldehydes in dry methanol and a catalytic amount of glacial acetic acid. The prepared compounds tested for in vitro Type II diabetes inhibition and antimicrobial (antibacterial and antifungal) activities employing α-amylase inhibition assay and the serial dilution method, respectively. Type II diabetes inhibitory assay results of all the tested derivatives revealed that precursor 3 (IC50 = 0.16 μM) and acetohydrazide 6i (IC50 = 0.38 μM) showed comparable activity with standard drug acarbose (IC50 = 0.15 μM). The derivatives 6i against B. subtilis and E. coli with MIC values of 0.0300 μmol/mL, compound 6c against S. aureus (MIC = 0.0312 μmol/mL) and compound 6e against P. aeruginosa (MIC = 0.0316 μmol/mL) exhibited remarkable antibacterial activity, however, compound 6b was found to be more active against the fungal strain C. albicans with MIC value of 0.0135 μmol/mL. All acetohydrazides (6a-j) showed greater potency against all strains tested than their precursors 1-4, which is also supported by the results of molecular docking analysis. Furthermore, no general trend for structure activity relationships was established for Type II diabetes inhibitory activity, nor antimicrobial activities of the tested hydrazones (6a-j).


icon graph This Abstract was viewed 901 times | icon graph Article PDF downloaded 388 times

How to Cite
(1)
Mor, S.; Sindhu, S.; Khatri, M.; Punia, R.; Jakhar, K. Synthesis, Type II Diabetes Inhibitory Activity, Antimicrobial Evaluation, and Docking Studies of N’-Arylidene-2-(7-methylbenzo[4,5]thiazolo[2,3-C] [1,2,4]triazol-3-yl)thio)acetohydrazides. Eur. J. Chem. 2022, 13, 426-434.

Article Details

Share
Links for Article


Crossref - Scopus - Google - European PMC
Crossref
Scopus
Google Scholar
Europe PMC
References

[1]. Kumar, P.; Duhan, M.; Kadyan, K.; Sindhu, J.; Kumar, S.; Sharma, H. Synthesis of novel inhibitors of α-amylase based on the thiazolidine-4-one skeleton containing a pyrazole moiety and their configurational studies. Medchemcomm 2017, 8, 1468-1476.
https://doi.org/10.1039/C7MD00080D

[2]. Cho, N. H.; Shaw, J. E.; Karuranga, S.; Huang, Y.; da Rocha Fernandes, J. D.; Ohlrogge, A. W.; Malanda, B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res. Clin. Pract. 2018, 138, 271-281.
https://doi.org/10.1016/j.diabres.2018.02.023

[3]. International Diabetes Foundation: Brussels IDF diabetes atlas. https://www.diabetesatlas.org (accessed August 24, 2022).

[4]. Wagman, A. S.; Boyce, R. S.; Brown, S. P.; Fang, E.; Goff, D.; Jansen, J. M.; Le, V. P.; Levine, B. H.; Ng, S. C.; Ni, Z.-J.; Nuss, J. M.; Pfister, K. B.; Ramurthy, S.; Renhowe, P. A.; Ring, D. B.; Shu, W.; Subramanian, S.; Zhou, X. A.; Shafer, C. M.; Harrison, S. D.; Johnson, K. W.; Bussiere, D. E. Synthesis, Binding Mode, and Antihyperglycemic Activity of Potent and Selective (5-Imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridyl amino)ethyl]amine Inhibitors of Glycogen Synthase Kinase 3. J. Med. Chem. 2017, 60, 8482-8514.
https://doi.org/10.1021/acs.jmedchem.7b00922

[5]. Keri, R. S.; Patil, M. R.; Patil, S. A.; Budagumpi, S. A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry. Eur. J. Med. Chem. 2015, 89, 207-251.
https://doi.org/10.1016/j.ejmech.2014.10.059

[6]. Patil, V. S.; Nandre, K. P.; Ghosh, S.; Rao, V. J.; Chopade, B. A.; Sridhar, B.; Bhosale, S. V.; Bhosale, S. V. Synthesis, crystal structure and antidiabetic activity of substituted (E)-3-(Benzo [d]thiazol-2-ylamino) phenylprop-2-en-1-one. Eur. J. Med. Chem. 2013, 59, 304-309.
https://doi.org/10.1016/j.ejmech.2012.11.020

[7]. Bashary, R.; Vyas, M.; Nayak, S. K.; Suttee, A.; Verma, S.; Narang, R.; Khatik, G. L. An insight of alpha-amylase inhibitors as a valuable tool in the management of type 2 diabetes mellitus. Curr. Diabetes Rev. 2020, 16, 117-136.
https://doi.org/10.2174/1573399815666190618093315

[8]. Chiasson, J.-L.; Josse, R. G.; Gomis, R.; Hanefeld, M.; Karasik, A.; Laakso, M.; STOP-NIDDM Trail Research Group Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002, 359, 2072-2077.
https://doi.org/10.1016/S0140-6736(02)08905-5

[9]. Larsson, D. G. J.; Flach, C.-F. Antibiotic resistance in the environment. Nat. Rev. Microbiol. 2022, 20, 257-269.
https://doi.org/10.1038/s41579-021-00649-x

[10]. Dhingra, S.; Rahman, N. A. A.; Peile, E.; Rahman, M.; Sartelli, M.; Hassali, M. A.; Islam, T.; Islam, S.; Haque, M. Microbial resistance movements: An overview of global public health threats posed by antimicrobial resistance, and how best to counter. Front. Public Health 2020, 8, 535668.
https://doi.org/10.3389/fpubh.2020.535668

[11]. Kim, M. B.; O'Brien, T. E.; Moore, J. T.; Anderson, D. E.; Foss, M. H.; Weibel, D.-L. B.; Ames, J. B.; Shaw, J. T. The synthesis and antimicrobial activity of heterocyclic derivatives of totarol. ACS Med. Chem. Lett. 2012, 3, 818-822.
https://doi.org/10.1021/ml3001775

[12]. Le Bozec, L.; Moody, C. J. Naturally occurring nitrogen-sulfur compounds. The benzothiazole alkaloids. Aust. J. Chem. 2009, 62, 639.
https://doi.org/10.1071/CH09126

[13]. Asif, M.; Imran, M. A mini-review on pharmacological importance of benzothiazole scaffold. Mini Rev. Org. Chem. 2021, 18, 1086-1097.
https://doi.org/10.2174/1570193X17999201127110214

[14]. Sharma, P. C.; Sinhmar, A.; Sharma, A.; Rajak, H.; Pathak, D. P. Medicinal significance of benzothiazole scaffold: an insight view. J. Enzyme Inhib. Med. Chem. 2013, 28, 240-266.
https://doi.org/10.3109/14756366.2012.720572

[15]. Mustafa, M.; Winum, J.-Y. The importance of sulfur-containing motifs in drug design and discovery. Expert Opin. Drug Discov. 2022, 17, 501-512.
https://doi.org/10.1080/17460441.2022.2044783

[16]. Scott, K. A.; Njardarson, J. T. Analysis of US FDA-approved drugs containing sulfur atoms. In Sulfur Chemistry; Springer International Publishing: Cham, 2019; pp. 1-34.
https://doi.org/10.1007/978-3-030-25598-5_1

[17]. Maddila, S.; Pagadala, R.; Jonnalagadda, S. 1,2,4-triazoles: A review of synthetic approaches and the biological activity. Lett. Org. Chem. 2013, 10, 693-714.
https://doi.org/10.2174/157017861010131126115448

[18]. Aggarwal, R.; Sumran, G. An insight on medicinal attributes of 1,2,4-triazoles. Eur. J. Med. Chem. 2020, 205, 112652.
https://doi.org/10.1016/j.ejmech.2020.112652

[19]. Peyton, L. R.; Gallagher, S.; Hashemzadeh, M. Triazole antifungals: a review. Drugs Today (Barc.) 2015, 51, 705-718.

[20]. H. Zhou, C.; Wang, Y. Recent researches in triazole compounds as medicinal drugs. Curr. Med. Chem. 2012, 19, 239-280.
https://doi.org/10.2174/092986712803414213

[21]. Russell, P. E. A century of fungicide evolution. J. Agric. Sci. 2005, 143, 11-25.
https://doi.org/10.1017/S0021859605004971

[22]. Láinez, M. J. A. Rizatriptan in the treatment of migraine. Neuropsychiatr. Dis. Treat. 2006, 2, 247-259.
https://doi.org/10.2147/nedt.2006.2.3.247

[23]. Stresser, D. M.; Turner, S. D.; McNamara, J.; Stocker, P.; Miller, V. P.; Crespi, C. L.; Patten, C. J. A high-throughput screen to identify inhibitors of aromatase (CYP19). Anal. Biochem. 2000, 284, 427-430.
https://doi.org/10.1006/abio.2000.4729

[24]. Sonsona, I. G.; Alegre-Requena, J. V.; Marqués-López, E.; Gimeno, M. C.; Herrera, R. P. Asymmetric organocatalyzed Aza-Henry reaction of hydrazones: Experimental and computational studies. Chemistry 2020, 26, 5469-5478.
https://doi.org/10.1002/chem.202000232

[25]. Wahbeh, J.; Milkowski, S. The use of hydrazones for biomedical applications. SLAS Technol. 2019, 24, 161-168.
https://doi.org/10.1177/2472630318822713

[26]. Thota, S.; Rodrigues, D. A.; Pinheiro, P. de S. M.; Lima, L. M.; Fraga, C. A. M.; Barreiro, E. J. N-Acylhydrazones as drugs. Bioorg. Med. Chem. Lett. 2018, 28, 2797-2806.
https://doi.org/10.1016/j.bmcl.2018.07.015

[27]. Kolb, P.; Ferreira, R. S.; Irwin, J. J.; Shoichet, B. K. Docking and chemoinformatic screens for new ligands and targets. Curr. Opin. Biotechnol. 2009, 20, 429-436.
https://doi.org/10.1016/j.copbio.2009.08.003

[28]. Stanzione, F.; Giangreco, I.; Cole, J. C. Use of molecular docking computational tools in drug discovery. Prog. Med. Chem. 2021, 60, 273-343.
https://doi.org/10.1016/bs.pmch.2021.01.004

[29]. Maia, E. H. B.; Assis, L. C.; de Oliveira, T. A.; da Silva, A. M.; Taranto, A. G. Structure-based virtual screening: From classical to artificial intelligence. Front. Chem. 2020, 8, 343.
https://doi.org/10.3389/fchem.2020.00343

[30]. Mor, S.; Sindhu, S. Synthesis, Type II diabetes inhibitory activity, antimicrobial evaluation and docking studies of indeno[1,2-c]pyrazol-4(1H)-ones. Med. Chem. Res. 2020, 29, 46-62.
https://doi.org/10.1007/s00044-019-02457-8

[31]. Mor, S.; Sindhu, S.; Nagoria, S.; Khatri, M.; Garg, P.; Sandhu, H.; Kumar, A. Synthesis, biological evaluation, and molecular docking studies of SomeN‐thiazolyl hydrazones and indenopyrazolones. J. Heterocycl. Chem. 2019, 56, 1622-1633.
https://doi.org/10.1002/jhet.3548

[32]. Mor, S.; Nagoria, S.; Sindhu, S.; Khatri, M.; Sidhu, G.; Singh, V. Synthesis of Indane-Based 1,5-Benzothiazepines Derived from 3-Phenyl-2,3-dihydro-1H-inden-1-one and Antimicrobial Studies Thereof: Synthesis and Antimicrobial Studies of Indane-Based 1,5-Benzothiazepines. J. Heterocycl. Chem. 2017, 54, 3282-3293.
https://doi.org/10.1002/jhet.2948

[33]. Mor, S.; Sindhu, S.; Khatri, M.; Singh, N.; Vasudeva, N.; Panihar, N. Synthesis, Type II Diabetes Inhibitory Activity, and Antimicrobial Tests of Benzothiazole Derivatives Bridged with Indenedione by Methylenehydrazone. Russian Journal of General Chemistry 2019, 89, 1867-1873.
https://doi.org/10.1134/S1070363219090226

[34]. Mor, S.; Sindhu, S.; Khatri, M.; Punia, R.; Sandhu, H.; Sindhu, J.; Jakhar, K. Antimicrobial evaluation and QSAR studies of 3,6-disubstituted-11H-benzo[5,6][1,4]thiazino[3,4-a]isoindol-11-ones. European Journal of Medicinal Chemistry Reports 2022, 5, 100050.
https://doi.org/10.1016/j.ejmcr.2022.100050

[35]. Mor, S.; Sindhu, S. Convenient and efficient synthesis of novel 11H-benzo[5,6][1,4]thiazino[3,4-a]isoindol-11-ones derived from 2-bromo-(2/3-substitutedphenyl)-1H-indene-1,3(2H)-diones. RSC Adv. 2019, 9, 12784-12792.
https://doi.org/10.1039/C9RA02403D

[36]. Abdelazeem, A. H.; Gouda, A. M.; Omar, H. A.; Alrobaian, M. Synthesis and Biological Evaluation of Novel Benzo[4,5]thiazolo[2,3-c][1,2,4] triazole Derivatives as Potential Anticancer Agents. Acta Poloniae Pharmaceutica 2018, 75, 625-636.

[37]. Xiao, Z.; Storms, R.; Tsang, A. A quantitative starch-iodine method for measuring alpha-amylase and glucoamylase activities. Anal. Biochem. 2006, 351, 146-148.
https://doi.org/10.1016/j.ab.2006.01.036

[38]. Yoshikawa, M.; Nishida, N.; Shimoda, H.; Takada, M.; Kawahara, Y.; Matsuda, H. Polyphenol Constituents from Salacia Species: Quantitative Analysis of Mangiferin with α-Glucosidase and Aldose Reductase Inhibitory Activities. Yakugaku Zasshi 2001, 121, 371-378.
https://doi.org/10.1248/yakushi.121.371

[39]. Mosaddik, M. A.; Haque, M. E. Cytotoxicity and antimicrobial activity of goniothalamin isolated from Bryonopsis laciniosa. Phytother. Res. 2003, 17, 1155-1157.
https://doi.org/10.1002/ptr.1303

[40]. Wood, J. L.; Roger, A. Organic Reactions, Volume 3; John Wiley & Sons: Nashville, TN, 1946.

[41]. Ajmal, M.; Mideen, A. S.; Quraishi, M. A. 2-hydrazino-6-methyl-benzothiazole as an effective inhibitor for the corrosion of mild steel in acidic solutions. Corros. Sci. 1994, 36, 79-84.
https://doi.org/10.1016/0010-938X(94)90110-4

[42]. Aboelmagd, A.; Ali, I. A. I.; Salem, E. M. S.; Abdel-Razik, M. Synthesis and antifungal activity of some s-mercaptotriazolobenzothiazolyl amino acid derivatives. Eur. J. Med. Chem. 2013, 60, 503-511.
https://doi.org/10.1016/j.ejmech.2012.10.033

[43]. Kumar, P.; Kadyan, K.; Duhan, M.; Sindhu, J.; Singh, V.; Saharan, B. S. Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents. Chem. Cent. J. 2017, 11, 115.
https://doi.org/10.1186/s13065-017-0344-7

[44]. Haraguchi, R.; Tanazawa, S.-G.; Tokunaga, N.; Fukuzawa, S.-I. Palladium-catalyzed formylation of arylzinc reagents withS-phenyl thioformate. Org. Lett. 2017, 19, 1646-1649.
https://doi.org/10.1021/acs.orglett.7b00447

[45]. Hitchcock, C. A.; Dickinson, K.; Brown, S. B.; Evans, E. G. V.; Adams, D. J. Interaction of azole antifungal antibiotics with cytochrome P-450-dependent 14α-sterol demethylase purified from Candida albicans. Biochem. J. 1990, 266, 475-480.
https://doi.org/10.1042/bj2660475

[46]. Hargrove, T. Y.; Garvey, E. P.; Hoekstra, W. J.; Yates, C. M.; Wawrzak, Z.; Rachakonda, G.; Villalta, F.; Lepesheva, G. I. Crystal structure of the new investigational drug candidate VT-1598 in complex with Aspergillus fumigatus sterol 14α-demethylase provides insights into its broad-spectrum antifungal activity. Antimicrob. Agents Chemother. 2017, 61, e00570-17.
https://doi.org/10.1128/AAC.00570-17

Supporting Agencies

Council of Scientific and Industrial Research (CSIR), CSIR No. 09/752(0060)/2016-EMR-I, New Delhi, India.
Most read articles by the same author(s)
TrendMD

Dimensions - Altmetric - scite_ - PlumX

Downloads and views

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...
License Terms

License Terms

by-nc

Copyright © 2025 by Authors. This work is published and licensed by Atlanta Publishing House LLC, Atlanta, GA, USA. The full terms of this license are available at https://www.eurjchem.com/index.php/eurjchem/terms and incorporate the Creative Commons Attribution-Non Commercial (CC BY NC) (International, v4.0) License (http://creativecommons.org/licenses/by-nc/4.0). By accessing the work, you hereby accept the Terms. This is an open access article distributed under the terms and conditions of the CC BY NC License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited without any further permission from Atlanta Publishing House LLC (European Journal of Chemistry). No use, distribution, or reproduction is permitted which does not comply with these terms. Permissions for commercial use of this work beyond the scope of the License (https://www.eurjchem.com/index.php/eurjchem/terms) are administered by Atlanta Publishing House LLC (European Journal of Chemistry).