Antiplasmodial activity, structure–activity relationship and studies on the action of novel benzimidazole derivatives

Abstract

Malaria cases and deaths keep being excessively high every year. Some inroads gained in the last two decades have been eroded especially due to the surge of resistance to most antimalarials. The search for new molecules that can replace the ones currently in use cannot stop. In this report, the synthesis of benzimidazole derivatives guided by structure–activity parameters is presented. Thirty-six molecules obtained are analyzed according to their activity against P. falciparum HB3 strain based on the type of substituent on rings A and B, their electron donor/withdrawing, as well as their dimension/spatial properties. There is a preference for electron donating groups on ring A, such as Me in position 5, or better, 5, 6-diMe. Ring B must be of the pyridine type such as picolinamide, other modifications are generally not favorable. Two molecules, 1 and 33 displayed antiplasmodial activity in the high nanomolar range against the chloroquine sensitive strain, with selectivity indexes above 10. Activity results of 1, 12 and 16 on a chloroquine resistance strain indicated an activity close to chloroquine for compound 1. Analysis of some of their effect on the parasites seem to suggest that 1 and 33 affect only the parasite and use a route other than interference with hemozoin biocrystallization, the route used by chloroquine and most antimalarials.

Facile Synthesis of Benzimidazoles via Oxidative Cyclization of Acyclic Monoterpene Aldehyde with Diamines: Studies on Antimicrobial and in Vivo Evaluation of Zebrafish

“…However, the MIC for Gram‐negative bacteria ranged from 128 to 512 μg, whereas that for Gram‐positive bacteria ranged from 64 to 512 μg. According to the present studies, [28] the benzimidazole compounds ( 3a – l ) with an unsubstituted phenyl ring or an electron‐withdrawing substitute are more efficient compared to one with an electron donating substituted group [29] …”

“…μg. According to the present studies, [28] the benzimidazole compounds (3a-l) with an unsubstituted phenyl ring or an electron-withdrawing substitute are more efficient compared to one with an electron donating substituted group. [29] Molecular docking is a computational method for figuring out how ligands interact with target proteins' active sites.…”

Synthesis, Characterization, Biological Activity, and Molecular Docking Study of Some New Sulfamethoxazole Derivatives.

“…1 H-NMR spectrums of compounds (a, 3bii), show important characteristics of chemical shifts (DMSO, δppm) as listed in Table 3. 1 H NMR spectrum of compound a shows a signal at δ2.25 ppm due to (3H) in methyl group(CH3), chemical shift seen at δ2.59 ppm due to (2H) in the CH2C=O group 22 . A chemical shift was noticed at δ3.43 ppm due to (2H) in the CH2NH group 22 .…”

“…It is exploited as an inhibitor for the growth of various sorts of bacteria including E. coli, Klebsiella, Enterobacter, Morganella morganii, Proteus mirabilis, and Proteus Vulgari. Sulfamethoxazole works together with trimethoprim to prevent folic acid formation, which stops the growth and reproduction of bacteria 1,2 . These therapeutic drugs have made significant contributions to increase average human life expectancy 3,4 .…”

Design, Synthesis, Antitumor, and Antiplasmodial Evaluation of New 7-Chloroquinoline–Benzimidazole Hybrids

“…There are several examples of benzimidazole-based compounds that have been approved as anti-cancer therapeutics or have been a part of clinical trials, such as binimetinib, bendamustine, and dovitinib [36][37][38]. Due to their ability to interact with various therapeutic targets, benzimidazole compounds have also been investigated as antimalarials [39,40].…”