Synthesis and antimicrobial activity of some novel hydrazide, benzochromenone, dihydropyridine, pyrrole, thiazole and thiophene derivatives

doi:10.1016/j.ejmech.2013.09.003

European Journal of Medicinal Chemistry

Volume 70, December 2013, Pages 419-426

https://doi.org/10.1016/j.ejmech.2013.09.003 Get rights and content

Highlights

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New heterocycles were synthesized incorporating oxygen, nitrogen and sulfur atoms.
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Compounds were screened for their antimicrobial activity.
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Some of the tested compounds exhibited promising activities.

Abstract

As a part of ongoing studies in developing new potent antimicrobial agents, a novel synthesis of 2-cyano-N-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)acetohydrazide (3) has been reported. The latter compound was reacted with different reagents to give new heterocyclic compounds. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, ¹H NMR, ¹³C NMR and mass spectral data. Representative compounds of the synthesized products were tested and evaluated as antimicrobial agents.

Graphical abstract

A variety of heterocyclic rings incorporating benzochromenone moiety were synthesized by reaction of 2-cyano-N-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)acetohydrazide (3) with different reagents to give new compounds 4–18. The compounds 9 and 17 showed highest antibacterial inhibition.

Introduction

Hydrazines and their derivatives constitute an important class of compounds that has found wide utility in organic synthesis [1], [2]. Also, they constitute an important class of compounds for new drug development [3]. A number of hydrazide–hydrazone derivatives have been claimed to possess interesting bioactivity such as antibacterial-antifungal [4], [5], [6], anticonvulsant [7], [8], anti-inflammatory [9], [10], antimalarial [11] and antituberculosis activities [12], [13]. Moreover, the coumarin nucleus is prevalent in numerous natural products and is extremely important in the chemistry of biological activities [14], which have found applications in treatment of antibacterial, antitumor, anti-inflammatory, antithrombotic, cardio protectors or enzymatic inhibitors antimicrobial and antifungal [15], [16], [17], [18], [19].

In view of the above-mentioned findings, and as a continuation of our effort to identify new candidates that may be valuable in designing new, potent, selective, and less toxic antimicrobial agents [20], [21], [22], [23], [24], [25], we report herein the synthesis of a series of hydrazide–hydrazones together with their use in a series of heterocyclic transformations and their evaluation as antimicrobial agents. This combination was suggested to investigate the influence of such hybridization and structure variation on the anticipated biological activities, hoping to add some synergistic biological significance to the target molecules.

Section snippets

Chemistry

The synthetic strategies adopted for the synthesis of the intermediates and to target compounds are depicted in Scheme 1, Scheme 2, Scheme 3. In Scheme 1, synthesis of 2-cyano-N-(1-(3-oxo-3H-benzo[f]chromen-2-yl)ethylidene)acetohydrazide (3), in analogy with the reported literature [26] by the reaction of 2-acetyl-3H-benzo[f]chromen-3-one (1) [27] and 2-cyanoacetohydrazide (2).

The assignment of structure 3 was supported by elemental analysis and spectral data. The IR spectrum displayed

Antimicrobial evaluation

All the newly synthesized compounds 3–18 were initially evaluated for in vitro antibacterial activity against Gram-positive bacteria (Staphylococcus aureus) (MTCC-96) and Gram-negative bacteria (Escherichia coli) (MTCC-443) and fungal (Candida albicans) using conventional Broth dilution method [29]. Ampicillin and Clotrimazole were used as reference drugs. The results were recorded for each tested compound as the average diameter of inhibition zones (IZ) of bacterial or fungal growth around the

Conclusion

Our attempts at exploring benzochromenone based pyran, pyridine, pyrrole, thiazole and thiophene derivatives have unexpectedly led to identification of a novel chemo type with substantial antimicrobial activity. Among the newly synthesized compounds 3–18, analogs 9 and 17 showed highest inhibition against nearly all of the tested bacteria, while all compounds were inactive against fungal strains. Results of antimicrobial activity clearly demonstrated that the presence of electron withdrawing

Experimental

Melting points were measured with a Gallenkamp apparatus are uncorrected. IR spectra were recorded KBr disc on a Mattson 5000 FTIR spectrophotometer at Microanalytical Unit, Faculty of Science, Mansoura University. The ¹H NMR and ¹³C NMR spectra were measured on Bruker WP AC 300 (300 MHz) in DMSO-d₆ as solvent, using tetramethylsilane (TMS) as an internal standard, and chemical shifts are expressed as δ_ppm. Mass spectra were determined on Finnigan Incos 500 (70 eV). Elemental analyses were

Antimicrobial evaluation

The disks of Whatman filter paper were prepared with standard size (5.0 mm diameter) and kept into 1.0 Oz screw capped wide mouthed containers for sterilization. These bottles are kept into hot air oven at a temperature of 150 °C. Then, the standard sterilized filter paper disks impregnated with a solution of the test compound in DMSO (1 mg/mL) were placed on nutrient agar plate seeded with appropriate test organism in triplicates. Standard conditions of 10⁶ CFU/mL (Colony Forming U/mL) and 10⁴

Acknowledgment

The authors are thankful to Department of Pharmacology, Faculty of Pharmacy, Mansoura University, Egypt for performing the antimicrobial evaluation.

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European Journal of Medicinal Chemistry

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Chemistry

Antimicrobial evaluation

Conclusion

Experimental

Antimicrobial evaluation

Acknowledgment

References (30)

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Eur. J. Med. Chem.

J. Organomet. Chem.

Biomaterials

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Bioorg. Med. Chem.

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Tetrahedron Lett.

Farmaco

Molecules

Spectrochim. Acta Part A Mol. Biomol. Spectrosc.

Pharmacol. Pharm.

Cited by (78)

Hydrazide-hydrazone/hydrazone as enabling linkers in anti-cancer drug discovery: A comprehensive review

Multistep synthesis of novel tris-Schiff bases – azobenzene hybrids as antimicrobial agents

Comparison on biological inspection, optimization, cyclic voltammetry, and molecular docking evaluation of novel bivalent transition metal chelates of Schiff Base pincer ligand

Elucidation for coordination features of N-(benzothiazol-2-yl)-3-oxo-3-(2-(3-phenylallylidene)hydrazineyl)propanamide on Co<sup>2+</sup>, Ni<sup>2+</sup>and Cu<sup>2+</sup>: Structural description, DFT geometry optimization, cyclic voltammetry and biological inspection

A comprehensive review on pyrazoline based heterocyclic hybrids as potent anticancer agents

A review on 1,4-dihydropyridines as anti-tuberculosis agent

Original articleSynthesis and antimicrobial activity of some novel hydrazide, benzochromenone, dihydropyridine, pyrrole, thiazole and thiophene derivatives

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Chemistry

Antimicrobial evaluation

Conclusion

Experimental

Antimicrobial evaluation

Acknowledgment

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Eur. J. Med. Chem.

J. Organomet. Chem.

Biomaterials

Eur. J. Med. Chem.

Bioorg. Med. Chem.

Eur. J. Med. Chem.

Eur. J. Med. Chem.

Tetrahedron Lett.

Farmaco

Molecules

Spectrochim. Acta Part A Mol. Biomol. Spectrosc.

Pharmacol. Pharm.

Original article
Synthesis and antimicrobial activity of some novel hydrazide, benzochromenone, dihydropyridine, pyrrole, thiazole and thiophene derivatives