Combinatorial Synthesis and Antibacterial Evaluation of an Indexed Chalcone Library

Abstract

A 120-membered chalcone library has been designed and prepared from six differently substituted acetophenones (A1-A6) and 20 benzaldehydes (B1-B20). The library was subjected to biological studies targeted against six bacterial strains. For the identification of the most-active member(s) of the library, the so-called indexed or positional-scanning method was applied. Six out of 26 sub-libraries, i.e., AL1-AL6, were synthesized by keeping the acetophenone moiety A fixed and using equimolar quantities of the 20 different benzaldehydes. The remaining 20 sub-libraries BL1-BL20 were prepared by keeping the benzaldehyde B component fixed and varying the six acetophenones (Table 1). The bactericidal activities of the resulting sub-libraries were tested and used as indices to the rows or columns of a two-dimensional matrix. Finally, parallel synthesis of 24 specific members with the highest-expected antibacterial activities, present in two sub-libraries, was carried out. These chalcones were screened again, and the results were exploited for establishing the structure-activity relationship (SAR) and the identification of the lead compound, which turned out to be 1,3-bis(2-hydroxyphenyl)prop-2-en-1-one (A2B2) in terms of activity towards Staphylococcus aureus and Bacillus subtilis (Tables 5-7).

Microwave assisted synthesis, antibacterial activity against Bordetella bronchiseptica of a library of 3΄-hydroxyaryl and heteroaryl chalcones and molecular descriptors-based SAR

“…H, 4-OH, 4-OMe, 4-F, 3-Cl, 4-Cl, 3-Br and 4-Me showed a linear correlation with bactericidal potency and fit in the regression line with value of r 2 =0.84 (Figure 2), the only exception being the NO 2 chalcones (18)(19)(20). This suppression of the activity by nitro group is also manifested in the series of thiophenesubstituted chalcones where the nitrochalcone (33) was found to be the least potent.…”

“…3-bromo and 3-chloro-have been found to possess high values of hydrophobicity constant (π), octanol-water partition coefficient (log P) and molar volume (Vm) with the exception of methoxy substituted chalcones. Moreover, the manifested bactericidal effect was also found to be facilitated by the presence of electron acceptors on the phenyl ring of chalcones of Set 1, the only exception being the nitro group which irrespective of its position on the phenyl ring suppressed the activity of all three regioisomeric chalcones (18)(19)(20). It may therefore be implied that the lipophilicity of the compounds appeared to be the main predictor of bactericidal activity.…”

“…We have reported earlier the design and synthesis of a 120-member library and its screening against a number of bacterial strains and the lead structure was identified through deconvolution based on positional scanning protocol. 18 Prompted by the findings and in continuation to our interest in the synthesis of biodynamic chalcones, 19,20 we synthesized a parallel library of 3-hydroxy-aryl and heteroaryl chalcones in order to study their bactericidal potential against B. bronchiseptica. Although we tested these compounds also against a number of other gram-positive and gram-negative bacterial strain namely, Micrococcus leuteus ATCC10240, Pseudomonas picketti ATCC 49129, Escherichia coli ATCC 15224, Enterobacter aerogenes ATCC 13048, and Salmonella setubal ATCC 19196, however, with the exception of B. bronchiseptica all the compounds were found to be generally inactive against these strains.…”

“…Agar well-diffusion method 18 was used for the study of the potential of these compounds against B. bronchiseptica as this bacterium can be grown easily in vitro on agar and broth medium, thereby making it possible to use this method to detect its susceptibility against any drug. A quantitative structure activity relationship has been interpreted by calculating a number of electronic parameters by the use of software package Molecular Operating Environment (MOE), 27 and very good SAR was established with a number of physicochemical determinants especially with E HOMO and log P. The selection of the substituents on the phenyl ring of the chalcones of Set 1 was made on the basis of their size, lipophilicity and electronic properties and they were changed systematically once at a time at 2-3-and 4-positions to get a set of regioisomers.…”

Uses of Isothiocyanate as Building Block in Syntheses of Triazole, Thiadiazole, Quinazoline, and Pyrimidine Systems of Agrochemical and Biological Activity

“…The synthesized compounds 3, 7, 8a, 9b and 8b 9c were tested for their antibacterial activity against two test organisms, Bacillus cereus (gram positive bacteria), Salmonela (gram negative bacteria) using the agar well-diffusion method (22) for studying the potential activities of these compounds using rifampicin (5 μg/disc) and ampicillin (10 μg/disc) as standard drugs. The antifungal activity of the synthesized compounds was tested against Aspergillus niger by a filter paper disc technique (23) .…”