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

Abstract

Microwave assisted synthesis of 33 membered parallel library of aryl-and heteroaryl chalcones was carried out by reaction of 3-hydroxyacetophenone with different substituted aryl-and heteroaryl aldehydes under Claisen-Schmidt conditions. The synthesized chalcones are significantly active against Bordetella bronchiseptica (ATCC 4617), gram negative respiratory pathogen that infects wide range of animals and human using cefixime as standard antibiotic as control. Tested compounds show moderate inhibitory activities (zone of inhibition 18.5-10.5 mm) compared to standard (zone of inhibition 13.0). All halogen substituted chalcones are most active members of the library while nitrochalcones and nitrogen containing heteroarylchalcones are least potent and 3-bromochalcone (16) was identified as lead structure of the library. Quantitative structure activity relationship was established to find dependency trend in sterms of bactericidal activity with number of molecular descriptors and some suggestive correlations of activity with these descriptors. Quantitative structure activity relationship was established using MOE software package showing good correlation of activity with various physicochemical parameters e.g. Hammett substituent constant σ, E HOMO , log P and molar volume Vm. It was observed that bactericidal potency of chalcones was dependent more on steric than on electronic descriptors. Chalcones with electron acceptors on phenyl ring and those with greater lipophilic character were expected to be stronger inhibitors of B. bronchiseptica with exception of nitrosubstituted chalcones. This study, therefore, facilitate design and synthesis of chalcones with higher potency to serve as potential inhibitors of B. bronchiseptica, thereby, helping to establish breakpoints for antimicrobial agents for which no systematic study is currently available.

Antibacterial Effects of Flavonoids and Their Structure-Activity Relationship Study: A Comparative Interpretation

“…(3 -Hydroxyphenyl)-3-(2-chlorophenyl)-2propen-1-one (11m), 1-(3 -Hydroxyphenyl)-3-(3-chlorophenyl)-2-propen-1-one (11n), 1-(3 -Hydroxyphenyl)-3-(4-chlorophenyl)-2-propen-1-one (11o) and 1-(3 -Hydroxyphenyl)-2-(3bromophenyl)-2-propen-1-one (11p) with MIC value of ≥0.2 mg/mL showed better antibacterial action than those derivatives which had polar hydroxy and methoxy groups such as 1-(3 -Hydroxyphenyl)-3-(2-hydroxyphenyl)-2-propen-1-one (11b), 1-(3 -Hydroxyphenyl)-3-(3-hydroxyphenyl)-2-propen-1-one (11c), 1-(3 -Hydroxyphenyl)-3-(4-hydroxyphenyl)-2-propen-1-one (11d), 1-(3 -Hydroxyphenyl)-3-(2-methoxyphenyl)-2-propen-1-one (11e), 1-(3 -Hydroxyphenyl)-3-(3-methoxyphenyl)-2-propen-1-one (11f), 1-(3 -Hydroxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one (11g), 1-(3 -Hydroxyphenyl)-3-(3,4-dimethoxyphenyl)-2-propen-1-one (11h), 1-(3 -Hydroxyphenyl)-3-(4-hydroxy,3-methoxyphenyl)-2-propen-1one (11i), and 1-(3 -Hydroxyphenyl)-3-(2-methyl-3,5-dimethoxyphenyl)-2-propen-1-one(11w) (MIC > 0.6 mg/mL). Furthermore, some polar compounds, such as 11h,i,w, displayed no activity[98].…”

Synthesis, Antimicrobial Activities, and Molecular Modeling Studies of Agents for the Sortase A Enzyme

“…and antimicrobial activity studies of compound T10 against Staphylococcus aureus by Talia et al were mentioned [38] . Besides, enzyme and cytotoxic activity studies of compounds T11 and T13 [39] and antimicrobial activity studies of T12 were reported [40] . Fandaklı et al.…”

“…In addition, biological activities of these analyzed compounds T1-2, T4-8, and T10-20 were reported in the literature, [30,[33][34][35][36][37][38][39][40][41][42][43][44][45] and the synthesis and activities of T3 and T9 compounds were performed for the first time in this study. Other studies were shown antioxidant and cytotoxic activity studies of T5 [34,35] and antibacterial and anti-inflammatory activity studies of T6 and T7 compounds.…”

“…[38] Besides, enzyme and cytotoxic activity studies of compounds T11 and T13 [39] and antimicrobial activity studies of T12 were reported. [40] Fandaklı et al reported enzyme inhibition activity studies of compound T13. [30] The antimicrobial activity of T14 against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans [41] and the cytotoxic and antibacterial activity of T15 were demonstrated.…”

New chalcone-3-O-glycoside derivatives: Synthesis and characterization

“…Compounds 3a–g were synthesized by the method described by Narender et al 21 NMR, MS, IR data, and melting point of the known compounds were consistent with those reported previously. 22–28…”