title: Design, synthesis, physicochemical studies, solvation, and DNA damage of quinoline-appended chalcone derivative: comprehensive spectroscopic approach toward drug discovery.
abstract: The present study epitomizes the design, synthesis, photophysics, solvation, and interaction with calf-thymus DNA of a potential antitumor, anticancer quinoline-appended chalcone derivative, (E)-3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one (ADMQ) using steady state absorption and fluorescence spectroscopy, molecular modeling, molecular docking, Fourier-transform infrared spectroscopy (FTIR), molecular dynamics (MD) simulation, and gel electrophoresis studies. ADMQ shows an unusual photophysical behavior in a variety of solvents of different polarity. The dual emission has been observed along with the formation of twisted intramolecular charge transfer (TICT) excited state. The radiationless deactivation of the TICT state is found to be promoted strongly by hydrogen bonding. Quantum mechanical (DFT, TDDFT, and ZINDO-CI) calculations show that the ADMQ is sort of molecular rotor which undergoes intramolecular twist followed by a complete charge transfer in the optimized excited state. FTIR studies reveals that ADMQ undergoes important structural change from its native structure to a β-hydroxy keto form in water at physiological pH. The concentration-dependent DNA cleavage has been identified in agarose gel DNA electrophoresis experiment and has been further supported by MD simulation. ADMQ forms hydrogen bond with the deoxyribose sugar attached with the nucleobase adenine DA-17 (chain A) and result in significant structural changes which potentially cleave DNA double helix. The compound does not exhibit any deleterious effect or toxicity to the E. coli strain in cytotoxicity studies. The consolidated spectroscopic research described herein can provide enormous information to open up new avenues for designing and synthesizing chalcone derivatives with low systematic toxicity for medicinal chemistry research.
authors: Department of Chemistry, Visvesvaraya National Institute of Technology , Nagpur, Maharashtra 440010, India.
authors: Himank
authors: H
authors: Kumar
authors: Anjan
authors: A
authors: Chattopadhyay
authors: R
authors: R
authors: Prasath
authors: Vinod
authors: V
authors: Devaraji
authors: Ritika
authors: R
authors: Joshi
authors: P
authors: P
authors: Bhavana
authors: Praveen
authors: P
authors: Saini
authors: Sujit Kumar
authors: SK
authors: Ghosh
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002417:Cattle; D002599:Chalcone / Q000031:analogs & derivatives*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D011789:Quantum Theory; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: C000597864:3-(anthracen-10-yl)-1-(6,8-dibromo-2-methylquinolin-3-yl)prop-2-en-1-one; D000873:Anthracenes; D000970:Antineoplastic Agents; D011804:Quinolines; D012997:Solvents; D002599:Chalcone; D004247:DNA; C427203:calf thymus DNA; C037219:quinoline