Design, synthesis, conformational and molecular docking study of some novel acyl hydrazone based molecular hybrids as antimalarial and antimicrobial agents

Abstract

BackgroundAcyl hydrazones are an important class of heterocyclic compounds promising pharmacological characteristics. Malaria is a life-threatening mosquito-borne blood disease caused by a plasmodium parasite. In some places, malaria can be treated and controlled with early diagnosis. However, some countries lack the resources to do this effectively.ResultsThe present work involves the design and synthesis of some novel acyl hydrazone based molecular hybrids of 1,4-dihydropyridine and pyrazole (5a–g). These molecular hybrids were synthesised by condensation of 1,4-dihydropyridin-4-yl-phenoxyacetohydrazides with differently substituted pyrazole carbaldehyde. The final compound (5) showed two conformations (the major, E, s-cis and the minor, E, s-trans) as revealed by NMR spectral data and further supported by the energy calculations (MOPAC2016 using PM7 method). All the synthesised compounds were screened for their in vitro antimalarial activities against chloroquine-sensitive malaria parasite Plasmodium falciparum (3D7) and antimicrobial activity against Gram positive bacteria i.e. Bacillus cereus, Gram negative bacteria i.e. Escherichia coli and antifungal activity against one fungus i.e. Aspergillus niger. All these compounds were found more potent than chloroquine and clotrimazole, the standard drugs.ConclusionsIn vitro antiplasmodial IC50 value of the most potent compound 5d was found to be 4.40 nM which is even less than all the three reference drugs chloroquine (18.7 nM), pyrimethamine (11 nM) and artimisinin (6 nM). In silico binding study of compound 5d with plasmodial cysteine protease falcipain-2 indicated the inhibition of falcipain-2 as the probable reason for the antimalarial potency of compound 5d. All the compounds had shown good to excellent antimicrobial and antifungal activities. Electronic supplementary materialThe online version of this article (10.1186/s13065-017-0344-7) contains supplementary material, which is available to authorized users.

Targeting Receptor Tyrosine Kinase VEGFR-2 in Hepatocellular Cancer: Rational Design, Synthesis and Biological Evaluation of 1,2-Disubstituted Benzimidazoles

“…Analysis of the 1 HNMR and 13 CNMR spectra of the obtained Schiff bases showed the duplication of signals which was rationalized to the presence of either E/Z geometrical isomers around the C=N or cis/trans conformers on the CO-NH ( Figure 5) [48]. However, it was reported that the Nacylhydrazones that results from the reaction between hydrazides and aromatic aldehydes favor the sterically less-hindered geometric E isomers A, B [49][50][51]. This result was also confirmed by our Xray study ( Figures 6 and 7).…”

“…It was found that compounds 17a and 17b displayed IC 50 = of 19.90 and 4.80 µM, respectively. From the obtained results, it is obvious that compound 17a (IC 50 = 19.90 µM) showed about ten-fold higher selectivity to the HepG2 cell line (IC 50 = 1.98 µM) over the normal HSF cell line, while compound 17b was found to be toxic to normal cells (IC 50 = 4.80 µM).…”

“…In series 17a-f, incorporation of a 3-(benzyloxy)phenyl group in 17a and 17b resulted in a potent cytotoxic activity (IC 50 50 = 20.18 µM).…”

“…In series 19a-d, introduction of phenoxy acetates resulted in a very weak cytotoxic activity (IC 50 = 71.73-133.39 µM). In series 22, both 22a and 22b were totally inactive (IC 50 > 100 µM).…”

Design, synthesis, and molecular docking of novel 2‐arylbenzothiazole multiangiokinase inhibitors targeting breast cancer

“…Different practical and computational experiments reported in the literature displayed the existence of the formed N ‐acylhydrazones in the sterically less hindered geometric E isomer and the duplication of signals was attributed to the presence of cis and trans conformers on CO–NH. [ 59–63 ] Based on the reported findings, the duplication of signals in the obtained nuclear magnetic resonance (NMR) spectra of 9a – n and 10a , b was rationalized to the presence of a mixture of cis and trans conformers C and D in ratios between 2:1 and 3:1 in the used NMR solvent (Figure 4; for further details see Section 4 and the Supporting Information Data).…”