Synthesis and biological screening of novel 2-morpholinoquinoline nucleus clubbed with 1,2,4-oxadiazole motifs

• Published in: European journal of medicinal chemistry Vol. 126; pp. 894 - 909
• Main Authors: Karad, Sharad C., Purohit, Vishal B., Thummar, Rahul P., Vaghasiya, Beena K., Kamani, Ronak D., Thakor, Parth, Thakkar, Vasudev R., Thakkar, Sampark S., Ray, Arabinda, Raval, Dipak K.
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 27-01-2017
• Subjects: 2-morpholinoquinoline based 1,2,4-oxadiazole; Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Infective Agents - metabolism; Anti-Infective Agents - pharmacology; Antimicrobial activity; Bacteria - drug effects; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Catalytic Domain; Chemistry Techniques, Synthetic; Cytotoxicity; Drug Evaluation, Preclinical; Fungi - drug effects; Microbial Sensitivity Tests; Molecular docking; Molecular Docking Simulation; Oxadiazoles - chemistry; Pharmacokinetic study; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - metabolism; Quinolines - pharmacology; Structure-Activity Relationship; Cytotoxicity; Antimicrobial activity; Pharmacokinetic study; 2-morpholinoquinoline based 1,2,4-oxadiazole; Molecular docking
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.12.016

Novel series of 2-morpholinoquinoline scaffolds (6a-n), containing the 1,2,4-oxadiazole and moiety, was designed and synthesized in good yield (76–86%). The synthesized compounds were screened for their preliminary in vitro antimicrobial activity against a panel of pathogenic strains of bacteria and fungi. Molecular docking and pharmacokinetic study were carried out for the prepared compounds. The cytotoxicity of the synthesized compounds was tested at different concentrations using bioassay of S. pombe cells at the cellular level. The effect of synthesized compounds on the DNA integrity of S. pombe was observed on agarose gel. Compounds 6d, 6e, 6g, 6h, 6j and 6n exhibited excellent antimicrobial potency as compared to the standard drugs (i.e Ampicillin, Norfloxacin, Chloramphenicol, Ciprofloxacin). Compounds 6d, 6e, 6g, 6k and 6n were found to have significant antifungal activity as compared to griseofulvin. Compounds 6f, 6i, 6k, 6l were found very less cytotoxic, while compounds 6d, 6e, 6g, 6h were found to exhibit maximum toxicity. The rest of the synthesized compounds were found to be moderately toxic.
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•The current study is concerned with design and synthesis of novel 2-morpholinoquinoline integrated 1,2,4-oxadiazole scaffolds.•Biological evaluation of the targeted compounds has been performed.•SAR study of 2-morpholinoquinoline based 1,2,4-oxadiazole derivatives has been discussed.•Compounds 6f, 6i, 6k and 6l were found very less cytotoxic.