Synthesis, Molecular Docking and Antimicrobial Activity of α, β‐Unsaturated Ketone Exchange Moiety for Chalcone and Pyrazoline Derivatives

Abstract

Bacterial diseases cause hazardous infections due to the occurrence of bacterial resistance. Drugs production to cure bacterial resistance from natural sources has become ineffective to execute the resisted bacteria due to the unsuitable binding interaction of active sites with the receptors. Drug link to natural products moieties such as chalcones and pyrazolines, which originated from plants extracts, has become attractive among researchers due to its significant pharmaceutical moiety. In this study a series of chalcone derivatives (1 a–d) has been synthesized via Claisen‐Schmidt condensation, followed by cyclization to form pyrazolines (2 a–d, 3 a–d). Fischer esterification of pyrazolines formed 4 a–d in moderate to good yield (42.91‐88.23 %). Antimicrobial activities of all the synthesized compounds were evaluated against Escherichia coli and Staphylococcus aureus via disc diffusion. Among all compounds, pyrazolines 3 c and 3 d showed the highest zone of inhibition (17 mm) compared to 1 a‐d (5‐11 mm) and standard ampicillin (11 mm). The exchange of α, β‐unsaturated carbonyl showed phenomenal increment in the biological activities. Structure activity relationship of 1 a, 1 d, 3 a and 3 d was analyzed via molecular docking of N‐terminal domain having deoxyribonucleic acid (DNA) binding protein (4pql) with excellent binding energy of −6.2, −6.6, −7.1 and −7.2 kcal/mol, respectively. This work is significant in designing new drugs with keto‐exchange relationship for medicinal industry.

An Overview on Synthesis and Biological Activity of Chalcone Derived Pyrazolines

“…Saba Farooq and Zainab Ngaini synthesized the series of chalcone (38 a‐d) firstly by the Claisen‐Schmidt condensation of 4‐acetyacetophenone and benzaldehyde in the presence of ethanolic NaOH, followed by cyclization with hydrazine derivative giving carboxylic pyrazoline derivatives ( 39 a – d ). For the synthesis of pyrazoline derivatives ( 41 a – d ), the chalcone and hydrazine derivatives ( 40 a – d ) were made to react in the presence of acetic acid and basic conditions [64] . (Scheme 13)…”

“…Among all the synthesized pyrazoline derivatives, compound ( 38 a – d ) with R=H, −F, and 4−Cl respectively showed excellent and higher inhibition against S.aureus with inhibition zone in the range of 14–17 mm. The highest bacterial inhibition against S.aureus and E.coli was shown by ( 40 c ) (R=4−Cl) and ( 40 d ) with inhibition zones in the range of 5–17 mm [64,65] …”

Microwave‐Assisted Synthesis, Antimicrobial Activities and Molecular Docking of Methoxycarboxylated Chalcone Derived Pyrazoline and Pyrazole Derivatives

“…The significant pharmacophore pyrazole and pyrazoline scaffolds were derived from chalconic precursors with methoxycarboxylated substituents. The significance of the methoxy group in the molecular network has been reported to increase the lipophilicity of the drug for superb biological activities, [37] whereby the carboxyl moiety is important to enhance the solubility of the drug [38] …”

One‐potandtwo‐potmethods for chalcone derived pyrimidines synthesis and applications

“…[151] Herein, we discuss comprehensive synthetic methods via one-pot and two-pot for the synthesis of pyrimidine derivatives from chalcone, a highly stable, cheap, commercially available starting material. Chalcone [152,153] is a common and excellent precursor employed in the synthesis of heterocycles (i.e., pyrazole, pyrazoline, [154][155][156] flavone, [157] cyclohexenone, [158] epoxide, [159] and pyrimidine [160,161] ). The review is a benefit to organic chemist researchers to design more potent unique compounds for pharmaceutical industries.…”