Pasha, Farhan Ahmad Muddassar, Muhhammad Beg, Yakub Cho, Seung Joo 2024-01-20T23:31:08Z 2024-01-20T23:31:08Z 2021-09-03 2008-05 1747-0277 https://pubs.kist.re.kr/handle/201004/133533 The phenoloxidase or tyrosinase is a key enzyme in insects, which is responsible for hydroxylation of tyrosine into o-quinones via o-diphenols. A series of benzaldehyde thiosemicarbazone, benzaldehyde and benzoic acid families were taken with their pragmatic pIC(50) values against phenoloxidase from pieris rapae (Lepidoptera) larvae. Density functional theory-based quantitative structure-activity relationship (QSAR) analyses were performed to speculate the key interaction. The most fitted four different QSAR models were identified and discussed. The softness, electrophilicity index, molar refractivity and log P were identified as best descriptors; however, the atomic values of softness and philicity obtained from Fukui function are more significant than global values. The study reveals that electrostatic and steric fields jointly contribute to activity. To gain further insight, the three-dimensional quantitative structure-activity relationship (3D-QSAR) analyses were performed using two molecular field techniques: comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The successful 3D-QSAR models were obtained from CoMFA (q(2) = 0.94, r(2) = 0.99, r(pred)(2) = 0.92) and CoMSIA (q(2) = 0.94, r(2) = 0.98, r(pred)(2) = 0/95). The CoMFA and CoMSIA results indicate that, a bulky and negative group around sulfur atom but a small and positive group around nitrogen atom might have good effects on activity. The ortho and meta positions of ring are favorable for small group. These QSAR models might be helpful to design the novel and potent inhibitors. English WILEY ATOMIC PHYSICOCHEMICAL PARAMETERS DIRECTED QUANTITATIVE STRUCTURE POSSIBLE DESCRIPTOR TYROSINASE ELECTROPHILICITY DERIVATIVES DOPAMINE DOCKING COMFA HELP DFT-based de novo QSAR of phenoloxidase inhibitors Article 10.1111/j.1747-0285.2008.00651.x 1 CHEMICAL BIOLOGY & DRUG DESIGN, v.71, no.5, pp.483 - 493 CHEMICAL BIOLOGY & DRUG DESIGN 71 5 483 493 scie scopus 000254810000008 2-s2.0-42049112803 Biochemistry & Molecular Biology Chemistry, Medicinal Biochemistry & Molecular Biology Pharmacology & Pharmacy Article ATOMIC PHYSICOCHEMICAL PARAMETERS DIRECTED QUANTITATIVE STRUCTURE POSSIBLE DESCRIPTOR TYROSINASE ELECTROPHILICITY DERIVATIVES DOPAMINE DOCKING COMFA HELP 3D-QSAR CoMFA CoMSIA DFT Drug design Phenoloxidase