Abstract

Herlina Rasyid¹, Bambang Purwono² and Ria Armunanto¹

DOI : http://dx.doi.org/10.13005/ojc/340517

Quantitative structure-activity relationship (QSAR) based on electronic descriptors had been conducted on 2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline analogues as anticancer using DFT/B3LYP method. The best QSAR equation described as follow: Log IC₅₀ = -11.688 + (-35.522×qC6) + (-21.055×qC10) + (-85.682×qC12) + (-32.997×qO22) + (-85.129 E_HOMO) + (19.724×E_LUMO). Statistical value of R² = 0.8732, r_m² = 0.7935, r²-r₀²/r² = 0.0118, PRESS = 1.5727 and F_calc/F_table = 2.4067 used as external validation. Atomic net charge showed as the most important descriptor to predict activity and design new molecule. Following QSAR analysis, Lipinski rules was applied to filter the design compound due to physicochemical properties and resulted that all filtered compounds did not violate the rules. Docking analysis was conducted to determine interaction between proposed compounds and EGFR protein. Critical hydrogen bond was found in Met769 residue suggesting that proposed compounds could be used to inhibit EGFR protein.

Docking Molecule; Electronic Descriptor; QSAR; Quinazoline

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