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https://ir.swu.ac.th/jspui/handle/123456789/12927| Title: | Synthesis, molecular docking, and QSAR study of sulfonamide-based indoles as aromatase inhibitors |
| Authors: | Pingaew R. Mandi P. Prachayasittikul V. Prachayasittikul S. Ruchirawat S. Prachayasittikul V. |
| Keywords: | 4 bromo n [2 (1h indol 3 yl)ethyl]benzenesulfonamide 4 fluoro n [2 (1h indol 3 yl)ethyl]benzenesulfonamide 4 trifluoromethyl n [2 (1h indol 3 yl)ethyl]benzenesulfonamide androstenedione aromatase aromatase inhibitor aspartic acid ellipticine indole derivative ketoconazole letrozole methionine n,n' [(2,2' [(4 nitrophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 bromobenzenesulfonamide) n,n' [(2,2' [(4 nitrophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 fluorobenzenesulfonamide) n,n' [[2,2' [(4 bromophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 trifluoromethylbenzenesulfonamide) n,n' [[2,2' [(4 cyanophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 chlorobenzenesulfonamide) n,n' [[2,2' [(4 cyanophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 fluorobenzenesulfonamide) n,n' [[2,2' [(4 cyanophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 trifluoromethylbenzenesulfonamide) n,n' [[2,2' [(4 fluorophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 bromobenzenesulfonamide) n,n' [[2,2' [(4 fluorophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 chlorobenzenesulfonamide) n,n' [[2,2' [(4 fluorophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 trifluoromethylbenzenesulfonamide) n,n' [[2,2' [(4 hydroxyphenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 trifluoromethylbenzenesulfonamide) n,n' [[2,2' [(4 nitrophenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 trifluoromethylbenzenesulfonamide) n,n' [[2,2' [(4 trifluoromethylphenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 bromobenzenesulfonamide) n,n' [[2,2' [(4 trifluoromethylphenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 chlorobenzenesulfonamide) n,n' [[2,2' [(4 trifluoromethylphenyl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 trifluoromethylbenzenesulfonamide) n,n' [[2,2' [(9 ethyl 9h carbazol 3 yl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 chlorobenzenesulfonamide) n,n' [[2,2' [(9h fluoren 2 yl)methylene]bis(1h indole 3,2 diyl)]bis(ethane 2,1 diyl)]bis(4 chlorobenzenesulfonamide) sulfonamide unclassified drug aromatase inhibitor indole derivative sulfonamide animal cell Article binding competition controlled study drug binding site drug cytotoxicity drug mechanism drug potency drug protein binding drug screening drug synthesis enzyme active site enzyme inhibition hydrogen bond IC50 molecular docking nonhuman quantitative structure activity relation animal cell survival chemical structure chemistry Chlorocebus aethiops dose response drug effects metabolism multivariate analysis synthesis Vero cell line Animals Aromatase Aromatase Inhibitors Cell Survival Cercopithecus aethiops Dose-Response Relationship, Drug Indoles Molecular Docking Simulation Molecular Structure Multivariate Analysis Quantitative Structure-Activity Relationship Sulfonamides Vero Cells |
| Issue Date: | 2018 |
| Abstract: | Thirty four of indoles bearing sulfonamides (11–44) were synthesized and evaluated for their anti-aromatase activities. Interestingly, all indole derivatives inhibited the aromatase with IC50 range of 0.7–15.3 μM. Indoles (27–36) exerted higher aromatase inhibitory activity than that of ketoconazole. The phenoxy analogs 28 and 34 with methoxy group were shown to be the most potent compounds with sub-micromolar IC50 values (i.e., 0.7 and 0.8 μM, respectively) without affecting to the normal cell line. Molecular docking demonstrated that the indoles 28, 30 and 34 could occupy the same binding site on the aromatase pocket and share several binding residues with those of the natural substrate (androstenedione), which suggested the competitive binding could be the mode of inhibition of the compounds. The most potent analog 28 could mimic H-bond interactions of the natural androstenedione with MET374 and ASP309 residues on the aromatase. QSAR model also revealed that the para-phenoxy indole (28) affords the higher value of electronegativity descriptor MATS6e as well as the higher inhibitory activity compared with that of the ortho-phenoxy compound (34). The study highlighted a series of promising indoles to be potentially developed as novel aromatase inhibitors for therapeutics. © 2017 Elsevier Masson SAS |
| URI: | https://ir.swu.ac.th/jspui/handle/123456789/12927 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85033552512&doi=10.1016%2fj.ejmech.2017.10.057&partnerID=40&md5=eedc5b18d0eeabd0844d07d1c860d3f6 |
| ISSN: | 2235234 |
| Appears in Collections: | Scopus 1983-2021 |
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