Characterisation ofPlasmodium falciparumaspartic protease inhibition by piperidine derivatives

Abstract

Piperidine derivatives are reported to exhibit a variety of pharmacological activities. In this article, synthesis and aspartic protease inhibitory activity of three nitrophenacyl derivatives of N-methyl-4-hydroxy piperidine are reported. Enzyme assays showed that the attachment of a nitro group in the benzene ring plays an important role in the inhibition of plasmepsin-II of Plasmodium falciparum. The compound 1-methyl-1-(4'-nitrophenacyl)-4-hydroxypiperidinium bromide (3), consisting of a nitro group at the para position, was the most active at the concentration of 1.0 µM. The activity of the compounds was evaluated through the observed orientation and diagrammatic representation of nitrophenacyl derivatives of 4-hydroxy piperidine.

Computer‐aided evaluation of targets and biological activity spectra for new piperidine derivatives

“…The prognostic data of the compounds presented in this article demonstrate the presence of significant effects on enzyme which correlates with the world research data. As well as in our study piperidine derivatives are capable of affecting various enzymes including kinases [31][32][33][34], viral proteases [35][36][37], hydrolases [38][39][40] and others [41][42][43][44][45], thereby realizing a wide range of activities. Based on the facts presented, the data obtained in the study may indicate the possible influence of compounds on the processes of inflammation, carcinogenesis, enzymatic activity of viruses, neuroprotection and other functional changes in the cardiovascular system and metabolism [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45].…”

A structure guided drug-discovery approach towards identification of Plasmodium inhibitors

“…of 1.0 mM with 22% inhibition in comparison to 100% inhibition by standard compound pepstatin. 34 New potent inhibitors of P. falciparum CQ resistant W2 strain were developed by adopting dual drug strategy. 7-Chloro-4-aminoquinoline ring system was introduced in the statine double drugs in order to improve the accumulation of PM inhibitors inside the food vacuole.…”