A review on diverse heterocyclic compounds as the privileged scaffolds in antimalarial drug discovery.

The upward extend of malaria collectively with the emergence of resistance against predictable drugs has put enormous pressure on public health systems to introduce new malaria treatments. Heterocycles play an important role in the design and discovery of new malaria active compounds. Heterocyclic compounds have attracted significant attention for malaria treatment because of simplicity of parallelization and the examining power with regard to chemical space. Introduction of a variety of heterocyclic compounds have enabled to maintain the high levels of antimalarial potency observed for other more lipophilic analogues whilst improving the solubility and the oral bioavailability in pre-clinical species. In this review, we present an overview of recent literature to provide imminent into the applications of different heterocyclic scaffolds in fighting against malaria.

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

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.

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

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.

Design, synthesis and characterization of fluoro substituted novel pyrazolylpyrazolines scaffold and their pharmacological screening.

A novel series of fluoro substituted pyrazolylpyrazolines 7a-l was synthesized in good to excellent yield (77-88%) from pyrazole chalcones 5a-d and substituted phenyl hydrazine hydrochlorides 6a-c under microwave irradiation. The newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic stains of bacteria and fungi, antituberculosis activity against Mycobacterium tuberculosis H37Rv and antimalarial activity against Plasmodium falciparum. Compounds 7a, 7b, 7g, 7h, 7j and 7k displayed excellent activity against P. falciparum stain as compared to quinine IC50 0.268. Good antitubercular activity was exhibited by compounds 7a, 7e, 7h and 7k. Some of them also exhibited superior antibacterial activity as compared to the first line drugs.