Original article
Synthesis, anti-bacterial and anti-fungal activities of some novel Schiff bases containing 2,4-disubstituted thiazole ring

https://doi.org/10.1016/j.ejmech.2009.11.008Get rights and content

Abstract

A series of arylidene-2-(4-(4-methoxy/bromophenyl) thiazol-2-yl) hydrazines (4az) and 1-(4-(4-methoxy/bromophenyl) thiazol-2-yl)-2-cyclohexylidene/cyclopentylidene hydrazines (5ab/6ab) were synthesized, characterized and screened for their antimicrobial activities. The structures of synthesized compounds were established by spectroscopic (FT-IR, 1H NMR, 13C NMR, Mass) and elemental analyses. Both the anti-bacterial and anti-fungal activities with MIC values of compounds were evaluated. The results of anti-bacterial screening reveal that among all the compounds screened eight compounds showed moderate to good anti-bacterial activity while ten of the newly synthesized compounds displayed good to excellent anti-fungal activity. Among the tested compounds, the most effective compounds with MIC value in the range of 6.25–25 μg/ml are 4a, 4n, 4z, 5a, 5b, 6a and 6b against three fungal strains viz. Candida albicans, Cryptococcus neoformans and Aspergillus flavus.

Graphical abstract

The synthesis, characterization and antimicrobial activity of a series of arylidene-2-(4-(4-methoxy/bromophenyl) thiazol-2-yl) hydrazines (4az) and 1-(4-(4-methoxy/bromophenyl) thiazol-2-yl)-2-cyclohexylidene/cyclopentylidene hydrazines (5ab/6ab) were reported.

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Introduction

Schiff bases have gained importance because of physiological and pharmacological activities associated with them. Compounds containing azomethine group (–Cdouble bondN–) in the structure are known as Schiff bases, which are usually synthesized by the condensation of primary amines and active carbonyl groups. Schiff bases are well known for their pharmacological properties as anti-bacterial, anti-fungal, anti-cancer and anti-viral agents [1], [2]. Similarly, the occurrence of thiazole ring system in numerous biologically active molecules has been recognized which plays an important role in animal and plant kingdom. Different thiazole bearing compounds possess activities such as anti-bacterial [3], anti-fungal [4], anti-inflammatory [5], antihypertensive [6], anti-HIV [7], antitumor [8], [9], [10], [11], antifilarial [10], [11], anticonvulsant [12], herbicidal, insecticidal, schistosomicidal and anthelmintic [13]. The presence of thiazole ring in vitamin B1 and its coenzyme play an important role as electron sink and for the decarboxylation of α-keto acids, respectively [14]. Many biologically active products, such as Bleomycin and Tiazofurin (antineoplastic agents) [15], Ritonavir (anti-HIV drug) [16], Fanetizole and Meloxicam (anti-inflammatory agents) [17], [18], Nizatidine (antiulcer agent) [19], imidacloprid (insecticide) and penicillin (antibiotic) are some examples of thiazole bearing products. Thiazole derivatives are also widely used for the synthesis of antibiotic sulphathiazole [20], and with polyoxygenated phenyl component they showed promising anti-fungal activity [21]. Thiazole nucleus as ligand of estrogen receptors [22] and also as novel class of antagonists for adenosine receptors [23] is known. Screening of 2,4-disubstituted thiazoles as latent pharmacophores for diacylhydrazine of SC-51089, a potential PGE2 antagonist have been reported [24]. The exciting results of 2,4-disubstituted thiazoles as a novel class of Src homology 2 (SH2) inhibitors for the treatment of osteoporosis and breast cancer have also been reported [25]. Synthesis of thiazole derivatives by various methods and their biological evaluation have been described by many researchers [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39]. Thus the thiazole nucleus has attracted much interest in the development of pharmacologically active compounds. Since the thiazole moiety seems to be a possible pharmacophore in various pharmacologically active agents, we decided to synthesize compounds with this functionality coupled with Schiff base as possible antimicrobial agents which could furnish better therapeutic results.

Section snippets

Chemistry

In the present work, arylidene-2-(4-(4-methoxy/bromophenyl) thiazol-2-yl) hydrazines (4az) and 1-(4-(4-methoxy/bromophenyl) thiazol-2-yl)-2-cyclohexylidene/cyclopentylidene hydrazines (5ab/6ab) were prepared by cyclization of thiosemicarbazone with substituted phenacyl bromide in accordance with the method described in the literature [34], [40], [41], [42], [43], [44], [45]. The synthetic route of compounds is outlined in Scheme 1. Compounds 5ab/6ab were prepared by above method by taking

Pharmacology

Anti-bacterial activity of newly synthesized compounds 4az/5ab/6ab was evaluated against various pathogenic bacterial strains (Gram-negative and Gram-positive) viz., Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Salmonella typhi (S. typhi), Pseudomonas aeruginosa (P. aeruginosa), Klebsiella pneumoniae (K. pneumoniae) and Vibrio cholerae (V. cholerae). Anti-fungal activity of the above compounds 4az/5ab/6ab was evaluated against fungal strains viz. Candida albicans (C.

Chemistry

The FT-IR spectra of Schiff bases of thiosemicarbazone (1am) showed absorption bands at 3120–3330 cm−1 for –NH– and –NH2, at 2950–3070 cm−1 for aromatic C–H and at 1590–1670 cm−1 for azomethine group (–CHdouble bondN–). The absence of absorption band at 1700–1750 cm−1 also confirms the conversion of –CHO/Cdouble bondO group to –CHdouble bondN– group. The nuclear magnetic resonance (1H NMR) spectra of the compounds were recorded in DMSO-d6/CDCl3 solvents and the structural assignments are given in Section 6. The 1H NMR spectra of

Conclusion

The novel Schiff bases containing 2,4-disubstituted thiazole ring were synthesized by cyclization of Schiff bases of thiosemicarbazone by treating with substituted phenacyl bromide and were studied for their antimicrobial activity. The results of anti-bacterial screening reveal that among all the compounds screened, compounds 4d, 4e, 4f, 4j, 4o and 4p showed moderate anti-bacterial activity while compound 4m and 4z displayed good anti-bacterial activity when compared with ciprofloxacin used as

Experimental protocols

All the chemicals and solvents used for this work were obtained from Merck (Germany), S.D. Fine (Mumbai), Hi-media (Mumbai) and Aldrich chemical company (U.S.A.). The chemicals purchased were of analytical reagent grade or were purified by standard methods prior to use [48]. Melting points of the synthesized compounds were determined in open-glass capillaries on Stuart-SMP10 melting point apparatus and are uncorrected. IR absorption spectra were recorded on Shimadzu FTIR-8400s using KBr pellets

Acknowledgements

The authors are grateful to The Head, Department of Chemistry, Faculty of Science, Banaras Hindu University (BHU),Varanasi, India for 1H NMR and 13C NMR spectroscopy and Indian Institute of Chemical Technology (IICT), Hyderabad for Mass spectroscopy. We, gratefully acknowledge for financial assistance given by University Grants Commission (UGC), New Delhi in the term of senior research fellowship to Mr. Sanjay Kumar Bharti.

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