Synthesis and Molecular Descriptor Characterization of Novel 4-Hydroxy-chromene-2-one Derivatives as Antimicrobial Agents

Abstract

Several novel 4-hydroxy-chromene-2-one derivatives 2b-16b were easily prepared through condensation reactions with microwave heating and characterized by elemental analysis, IR, 1H-NMR and mass spectrometry. Geometry optimization of these compounds was executed by PM3, PM5 and Minimize Energy methods to describe them via molecular descriptors. The antimicrobial activity of the synthesized compounds was evaluated against different microbial strains using two different methods: the diffusion method and the micro-dilution method. All data indicated that the products possess antimicrobial activity which depends on the nature of substituent attached to the benzopyran moiety. In general, after 24 h the MIC values of most tested coumarins was 0.13 mg/mL, but compounds 1 and 6b displayed the strongest antimicrobial activity on the tested cultures of bacteria after 48 h. Compound 13b has the strongest growth inhibitory potential on fungus C. albicans, tested by diffusion method, with an inhibition zone of 30-37 mm at a concentration of 150 µg/mL. The conclusion of this experiment is that the synthesized compounds have varied and different influence on different classes of bacteria and the fungus C. albicans.

Synthesis and biological evaluation of novel 3-substituted amino-4-hydroxylcoumarin derivatives as chitin synthase inhibitors and antifungal agents

“…In recent studies, the coumarin heterocycles (Figure 2), as antimicrobial agents, have attracted extensive interest. For instance, the 7-substituted coumarin (II) showed a moderate efficacy (minimal inhibitory concentration, MIC ¼ 125 lg/mL) against Cryptococcus neoformans 32 ; the 4-chloro-3-phenylimino coumarin (III) exhibited moderate antifungal activity (MIC ¼ 15 lg /mL) against Aspergillus niger and Candida albicans in comparison with fluconazole 33 ; the Imidazolethione coumarin hydrazide derivatives (IV) had good antibacterial activity against Escherichia coli with inhibitory zone diameter of 32 mm in 25 lg/mL 34 and the 4-azidomethyl coumarin sulfonamides derivatives (V) showed excellent antifungal efficacies against C. albicans, A. niger and Fusarium oxysporum with MIC values of 1-4 lg/ mL, which were 2-8 times more potent than fluconazole (MIC ¼ 8 lg/mL) 35 . Thus, the coumarin is a versatile fragment used to design the novel compounds with pharmacological activity.…”

3-Acetyl-4-hydroxycoumarin: Synthesis, reactions and applications

“…Different carbonyl, ester and cyano derivatives 23 were used in the condensations with 1 to achieve structural variety in the produced coumarins 24 (Mladenovic et al, 2009) (Scheme 16).…”

“…Recently several workers have reported the synthesis of 28 via the condensation reaction of 1 with various amines 27 either under conventional heating (Bavishi et al, 2013;Jevtic et al, 2013) or under microwave irradiation (Mladenovic et al, 2009;Vukovic et al, 2010a,b) (Scheme 19). It is worth to note that the yield has been significantly increased using reaction under microwave irradiation particularly in case of imino derivatives with p-nitrophenyl (92%), m-nitrophenyl (97%) and pentanoic acid substituent (87%).…”

“…3-Acetyl-4-hydroxycoumarin represents the core structure of several natural products and is the central pharmacophore found in a number of medicinal agents such as antimicrobial, antifungal and antioxidant agents (Mladenovic et al, 2009;AlAyed, 2011). These special properties turn 3-acetyl-4-hydroxycoumarin into very interesting targets to organic chemists, and several strategies for their synthesis were developed including acylation, bromination, metalation, and Claisen-Schmidt condensation.…”

Comparative Studies of Chromen Derivatives by Using Numerical Methods

“…The work on 4-hydroxy-chromen-2-one as antimicrobial agents has been cited by Maladenovic et al [19]. We have studied the different properties of some coumarin systems by molecular dynamics by Mesli et al [20,21] as well as work of Mahboub et al [22].…”