The control of antimicrobial resistance (AMR) seems to have come to a dead end. The major consequences of the use and abuse of antibacterial drugs are the development of resistant strains due to genetic mutability of both pathogenic and nonpathogenic microorganisms. We, herein, report the synthesis, characterization and biological activities of coumarin-thiazole-pyrazole (CTP) molecular hybrids with an effort to explore and overcome the increasing antimicrobial resistance. The compounds were characterized by analyzing their IR, Mass, 1H and13C NMR spectral data and elemental analysis. The in vitro antimicrobial activity of the synthesized compounds was investigated against various pathogenic strains; the results obtained were further explained with the help of DFT and molecular orbital calculations. Compound 1b and 1f displayed good antimicrobial activity and synergistic effects when used with kanamycin and amphotericin B. Furthermore, in vitro cytotoxicity of compounds 1b and 1f were studied against HeLa cells (cervical cancer cell) and Hek-293 cells. The results of molecular docking study were used to better rationalize the action and prediction of the binding modes of these compounds.

Postprandial hyperglycemia can be controlled by delaying the absorption of glucose resulting from carbohydrate digestion. α-Amylase is the initiator of the hydrolysis of polysaccharides, and therefore developing α-amylase inhibitors can lead to development of new treatments for metabolic disorders like diabetes mellitus. In the present work, we set out to rationally develop α-amylase inhibitors based on the thiazolidine-4-one scaffold. The structures of all these newly synthesized hybrids were confirmed by spectroscopic analysis (IR, H-NMR, MS). The appearance of two sets of signals for some protons inH NMR revealed the existence of a mixture of 2,5 (37.1-42.0%) and 2,5 isomers (58.4-62.8%), which was further supported by DFT studies. All the newly synthesized compounds have potential inhibitory properties as revealed through α-amylase inhibition activity. Compound at 100 μg mL concentration showed a remarkable inhibition of 90.04%. α-amylase inhibition was further supported by docking studies of compound against the active site of human pancreatic α-amylase (PDB ID: ; 2QV4). The docking studies revealed that the bonding interactions found between and human pancreatic α-amylase are similar to those responsible for α-amylase inhibition by acarbose.

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.

Molecular hybrids based on thiazolidin‐4‐one and pyrazolyl pharmacophore (THZP) as new antidiabetic agents were synthesized. Two sets of signals came into view in 1H NMR of THZP8‐THZP14 exhibited the presence of a configurational isomeric mixture of 2E,5Z (38.24%‐41.58%) and 2Z,5Z isomers (58.42%‐61.76%), which was further endorsed by density functional theory (DFT) studies. All the compounds exhibit promising nonlinear optical properties (NLO). Further, the biological potential of THZPs was explored in terms of α‐amylase and α‐glucosidase inhibition. DFT‐based descriptors were calculated to describe the reactivity, and a relationship was developed with biological activities. THZP9 and THZP14 showed remarkable inhibition of α‐amylase and α‐glucosidase with IC50 9.90μM and 4.84μM, respectively, as compared with standard drug acarbose.

No abstract

No abstract

No abstract

No abstract