Novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: Synthesis, antibacterial, antitubercular and antimalarial activities

• Published in: European journal of medicinal chemistry 2016-04, Vol.112, p.270-279
• Main Authors: Karad, Sharad C., Purohit, Vishal B., Thakor, Parth, Thakkar, Vasudev R., Raval, Dipak K.
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents - chemical synthesis; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antimalarials - chemistry; Antimalarials - pharmacology; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Bacteria - drug effects; Bacterial Infections - drug therapy; Biological evaluation; Cytotoxicity; Fungi - drug effects; Humans; Malaria, Falciparum - drug therapy; Microbial Sensitivity Tests; Microwave promoted reactions; Mycobacterium tuberculosis - drug effects; Mycoses - drug therapy; Plasmodium falciparum - drug effects; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Quinoline-pyrazoline analogs; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Structure-Activity Relationship; Tuberculosis - drug therapy
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.02.016

A series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. The newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against Mycobacterium tuberculosis H37Rv and antimalarial activity against Plasmodium falciparum. Most of them exhibited significant antibacterial activity as compared to the first line drugs. Compounds 6a and 9d were found to possess excellent antibacterial activity potency as compared to ampicillin (286 μM), chloramphenicol (154 μM) and ciprofloxacin (150 μM). In antifungal screening, against Candida albicans, compounds 6c, 7c, 8a, 8b, 8c and 9b showed significant activity as compared to griseofulvin (1147 μM). Compounds 8b, 6b, 9d, 6a, 9b, 7b and 8a displayed brilliant activity against P. falciparum strain as compared to chloroquine (IC50 0.062 μM) as well as quinine (IC50 0.826 μM). Compounds 6d, 7b, 8b, 9c and 9d exhibited superior antitubercular activity. Among them 8b was found to be equipotent to rifampicin with 95% inhibition. The cytotoxicity of the synthesized compounds was tested using bioassay of Schizosaccharomyces pombe cells at cellular level. [Display omitted] •Morpholinoquinolines clubbed with pyrazoline were synthesized under microwave.•6a and 9d exhibited excellent antibacterial activity.•6c, 7c, 8a, 8b, 8c and 9b showed significant activity against Candida albicans.•Antitubercular activity of 8b was found to be equipotent to rifampicin.•Seven compounds displayed brilliant antimalarial activity against Plasmodium falciparum.