Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation.

Cationic surfactants based on phenylalanine (CnPC3NH3Cl) and tryptophan (CnTC3NH3Cl) were synthesized using renewable raw materials as starting compounds and a green synthetic procedure. The synthesis, acid-base equilibrium, aggregation properties, and antibacterial activity were investigated. Conductivity and fluorescence were used to establish critical micelle concentrations. Micellization of CnPC3NH3Cl and CnTC3NH3Cl occurred in the ranges of 0.42-16.2 mM and 0.29-4.6 mM, respectively. Since those surfactants have some acidic character, the apparent pKa was determined through titrations, observing increasing acidity with increasing chain length and being slightly more acidic with the phenylalanine than the tryptophan derivatives. Both families showed promising antibacterial efficacy against eight different bacterial strains. Molecular docking studies against the enzyme peptidoglycan glycosyltransferase (PDB ID:2OQO) were used to investigate the potential binding mechanism of target surfactant molecules. According to small angle X-ray scattering (SAXS) results, the surfactants incorporate into DPPC (Dipalmitoyl Phosphatidyl Choline) bilayers without strong perturbation up to high surfactant concentration. Some of the C12TC3NH3Cl/DPPC formulations (40%/60% and 20%/80% molar ratios) exhibited good antibacterial activity, while the others were not effective against the tested bacteria. The strong affinity between DPPC and surfactant molecules, as determined by the DFT (density functional theory) method, could be one of the reasons for the loss of antibacterial activity of these cationic surfactants when they are incorporated in vesicles.

Biological, toxicological and molecular docking evaluations of isoxazoline-thiazolidine-2,4-dione analogues as new class of anti-hyperglycemic agents.

In this work, three isoxazoline-thiazolidine-2,4-dione derivatives were synthesized and characterized by FT-IR, 1H-NMR, 13C-NMR and ESI-MS spectrometry. All compounds have been investigated for their α-amylase and α-glucosidase inhibitory activities. In vitro enzymatic evaluation revealed that all compounds were inhibitory potent against α-glucosidase with IC50 values varied from 40.67 ± 1.81 to 92.54 ± 0.43 µM, and α-amylase with IC50 in the range of 07.01 ± 0.02 to 75.10 ± 1.06 µM. One of the tested compounds were found to be more potent inhibitor compared to other compounds and standard drug Acarbose (IC50 glucosidase= 97.12 ± 0.35 µM and IC50 amylase= 2.97 ± 0.01 µM). All compounds were then evaluated for their acute toxicity in vivo and shown their safety at a high dose with LD > 2000mg/kg BW. A cell-based toxicity evaluation was performed to determine the safety of compounds on liver cells, using the MTT assay against HepG2 cells, and the results shown that all compounds have non-toxic impact against cell viability and proliferation compared to reference drug (Pioglitazone). Furthermore, the molecular homology analysis, SAR and the molecular binding properties of compound with the active site of α-amylase and α-glucosidase were confirmed through computational analysis. This study has identified the inhibitory potential of a new class of synthesized isoxazoline-thiazolidine-2,4-dione derivatives in controlling both hyperglycemia and type 2 diabetes mellitus without any hepatic toxicity.Communicated by Ramaswamy H. Sarma.

Antifungal activity of amino-alcohols based cationic surfactants and in silico, homology modeling, docking and molecular dynamics studies against lanosterol 14-α-demethylase enzyme.

Fungi are being responsible for causing serious infections in humans and animals. The opportunistic microorganisms provoke environmental contaminations in health and storage facilities to represent a serious concern to health security. The present work investigates the antifungal activity of two amino-alcohols based cationic surfactants such as CnEtOH, CnPrOH (with n = 14 and 16 are the carbon numbers of alkyl chain and EtOH = Ethanol and PrOH = Propanol) against a collection of different Candida species (Candida tropicalis, Candida albicans, Candida auris, Cyberlindnera jadinii, Candida parapsilosis, Candida glabrata and Candida rugosa) respectively. The amino-alcohols based cationic surfactants exhibited good antifungal activity against all Candida strains tested with minimum inhibitory concentrations (MIC) ranging from 0.002 to 0.30 mM. The MIC evaluation shows an increase as a function of the hydrophobicity of all inhibitors against the majority of the Candida strains tested. The different location of the alcoholic OH function in the polar head shows the influence on the availability of N+ responsible for electrostatic interactions with the candidate's cell walls, which remains a very important step in the mode of action of quaternary ammonium cationic surfactants. Hence, a 3D structure of lanosterol 14-α-demethylase enzyme from C. auris was constructed by homology modeling using an online SWISS-MODEL server. The predicted model was analyzed by serval servers. Furthermore, a molecular docking study was carried out to better understand the binding mechanism of lanosterol homologous protein with surfactant ligands. Then, the docked complexes lanosterol-surfactants were refined by the molecular dynamic simulation to analyze their interaction behavior during the simulation.Communicated by Ramaswamy H. Sarma.

Synthesis, α-glucosidase and α-amylase inhibitory activities, acute toxicity and molecular docking studies of thiazolidine-2,4-diones derivatives.

In the present study, a series of thiazolidine-2,4-diones derivatives (3a-3e) and (4a-4e) were synthesized and characterized by 1H NMR, 13C NMR and ESI-MS spectrometry. All compounds were screened for their α-glucosidase and α-amylase inhibitory activities. In vitro biological investigations revealed that most of compounds were active against α-glucosidase with IC50 values in the range of 43.85 ± 1.06 to 380.10 ± 1.02 µM, and α-amylase with IC50 in the range of 18.19 ± 0.11 to 208.10 ± 1.80 µM. Some of the tested compounds were found to be more potent inhibitors than the clinical drug Acarbose (IC50glucosidase = 97.12 ± 0.35 µM and IC50amylase = 2.97 ± 0.004 µM). The lead compounds were evaluated for their acute toxicity on Swiss mice and found to be completely non-toxic with LD > 2000 mg/kg BW. Furthermore, the Structure-activity relationship (SAR) and the binding interactions of all compounds with the active site of α-glucosidase and α-amylase were confirmed through molecular docking and stabilizing energy calculations. This study has identified the inhibitory potential a new class of synthesized thiazolidine-2,4-diones in controlling both hyperglycemia and type 2 diabetes mellitus. Furthermore, the theoretical binding mode of the target molecules was evaluated by molecular docking studies against the 3D Crystal Structure of human pancreatic α-amylase (PDB ID: 1B2Y) and α-glucosidase (PDB ID: 3W37)Communicated by Ramaswamy H. Sarma.