SYNTHESIS, IN VITRO ANTIBACTERIAL, TOXICITY AND MOLECULAR DOCKING ANTICANCER ACTIVITY OF NOVEL N-[(2-CHLOROQUINOLIN-3-YL) METHYLIDENE]-2-ANILINE SCHIFF'S BASES

Objective: Synthesis of N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j) and to study their in vitro antibacterial activity and in silico study towards cancer and malarial proteins. Methods: Various N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j) were synthesized by using 2-chloro-3-formyl quinoline and different anilines in presence of acetic acid as catalyst. All the new compounds were characterized by 1H-NMR, [13]C-NMR and LCMS analysis. The compounds 3a-j was subjected to antibacterial activity. In silico molecular properties were predicted using various online cheminformatic tools, the binding interactions with Human DNA topoisomerase I and Plasmodium falciparum lactate dehydrogenase proteins was studied through molecular docking and Irinotecan and mefloquine were used as reference drugs. Results: Fairly good yield of N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j) were synthesized by convenient and economical procedure. The preliminary in silico pharmacokinetics study reveals that the compounds 3a-j shows excellent drug like property. The toxicity profile of compounds 3a-h was found safe. The compounds 3a-j was exhibited promising MIC values against the both S. aureus and E. coli. Similarly the docking results predict that the compound 3d shown highest interaction by forming two hydrogen bonds against the cancer protein with the interaction energy-20.696 kcal/mol. Compound 3c exhibits highest dock score of-45.703 kcal/mol with two hydrogen bonds against malarial protein. Conclusion: From the results of docking studies of N-[(2-chloroquinolin-3-yl) methylidene]-2-aniline schiff bases (3a-j), it has been concluded that the compounds were found to exhibit multifunctional lead property, hence these compounds are worth to be considered as potential lead molecules for further study

SYNTHESIS AND MOLECULAR DOCKING STUDY OF 2-ARYL/HETEROARYL-6-CHLOROQUINOLINE-4-CARBOXYLIC ACIDS WITH PLASMODIUM LDH RECEPTOR PROTEIN

Objective: Synthesis and in silico molecular docking studies of 2-aryl/heteroaryl-quinoline-4-carboxylic acid derivatives (3a-j) with plasmodium LDH receptor protein.Methods: The 2-aryl/heteroaryl-quinoline-4-carboxylic acids (3a-j) were obtained by Pfitzinger reaction. Ligands (3a-j) interaction with plasmodium LDH receptor protein was studied through molecular docking method.Results: Good yields of 2-aryl/heteroaryl-quinoline-4-carboxylic acid derivatives (3a-j) were obtained by convenient and economical procedure. Their structures were confirmed by 1H NMR, 13C NMR, and MS spectral analysis. The binding site analysis of the synthesized compounds (3a-j) with plasmodium LDH receptor that are responsible for malaria parasite response was evaluated through molecular docking study. The results reveal that the ligand 3d shows maximum of five hydrogen bonding interactions with binding energy -9.05 kcal/mol, shown to be a promising lead molecule to inhibit Plasmodium LDH receptor.Conclusion: The docking studies of newly synthesized 2-aryl/heteroaryl-quinoline-4-carboxylic acids were found to be very useful ligands for antimalarial therapy particularly on Plasmodium LDH protein. However the installation of still many appropriate substitutions on quinoline moiety would lead to identification of novel antimalarial compounds that ascertained via molecular docking is underway in our lab

Synthesis and cytotoxic studies of 2, 3-dimethylindoles and tetrahydrocarbazoles

Objective: The objective of this study was to report the synthesis of 2,3-dimethylindoles and tetrahydrocarbazoles via Fisher indole synthesis and evaluation of their the anticancer properties. Methods: A simple and more efficient method for the synthesis of 2,3-dimethylindoles and tetrahydrocarbazoles has been described using Phenylhydrazine hydrochlorides and different cyclic and acyclic ketones in presence of antimony phosphate as catalyst in methanol solvent at reflux temperature in one pot reaction. Results: The synthesized compounds were characterized by spectroscopic techniques (1H NMR, 13C NMR, LC-MS and elemental analysis) and tested for anticancer activity against five different cell lines such as kidney adenocarcinoma (ACHN), pancreas carcinoma (Panc1), lung carcinoma (GIII) (Calu1), non-small cell lung carcinoma (H460), colon cancer cell (HCT116) and normal breast epithelium (MCF10A) cell lines. The results indicated that the compounds 3a and 3b exhibit promising activity against both lung carcinoma and pancreas carcinoma cell line with IC50 value 2.7, 3.1, 2.8 and 3.2nM. Whereas compound 5d shows high activity against lung carcinoma cell line alone with IC50 2.5nM and remaining derivatives exhibited good to moderate activity. Conclusion: The differently substituted 2,3-dimethylindoles and tetrahydrocarbazoles have reported to posses significant activity. Since their synthesis made very simple in this report, the method of synthesis and promising results of 2,3-dimethylindoles and tetrahydrocarbazoles on different cancer cell lines opens an opportunity among researcher for their further study of such moieties

Crystal structure of ethyl 6-bromo-2-[(E)-2-phenylethenyl]quinoline-4-carboxylate

In the title compound, C20H16BrNO2, the dihedral angle between the quinolone ring system mean plane (r.m.s. deviation = 0.018 Å) and the phenyl ring bridged by the ethynyl group, is 25.44 (14)°. There is an intramolecular C—H...O hydrogen bond forming an S(6) ring motif. In the crystal, molecules are linked via C—H...O hydrogen bonds forming chains propagating along the b-axis direction