Identification of Potential Antitubulin Agents with Anticancer Assets from a Series of Imidazo[1,2-a]quinoxaline Derivatives: In Silico and In Vitro Approaches

Abstract

Computer-aided drug design is a powerful and promising tool for drug design and development, with a reduced cost and time. In the current study, we rationally selected a library of 34 fused imidazo[1,2-a]quinoxaline derivatives and performed virtual screening, molecular docking, and molecular mechanics for a lead identification against tubulin as an anticancer molecule. The computational analysis and pharmacophoric features were represented as 1A2; this was a potential lead against tubulin, with a maximized affinity and binding score at the colchicine-binding site of tubulin. The efficiency of this lead molecule was further identified using an in vitro assay on a tubulin enzyme and the anticancer potential was established using an MTT assay. Compound 1A2 (IC50 = 4.33–6.11 µM against MCF-7, MDA-MB-231, HCT-116, and A549 cell lines) displayed encouraging results similar to the standard drug colchicine in these in vitro studies, which further confirmed the effectiveness of CADD in new drug developments. Thus, we successfully applied the utility of in silico techniques to identify the best plausible leads from the fused azaheterocycles.

Chemistry, Synthesis, and Structure Activity Relationship of Anticancer Quinoxalines

“…Table 3. The selected quinoxaline model (25), the designed quinoxaline derivatives (26)(27)(28)(29)(30), and their computed VEGFR-2 inhibitive activities. GATS5e (Geary autocorrelation-lag 5/weighted by Sanderson electronegativities), GATS3i (Geary autocorrelation-lag 3/weighted by Sanderson electronegativities), GATS8i (Geary autocorrelation-lag 8/weighted by Sanderson electronegativities), SpMax8_Bhs (the largest absolute eigenvalue of Burden modified matrix-n 8/weighted by relative I-state), VR2-Dt (normalized Randic-like eigenvector-based index from Detourn matrix).…”

“…It is a low-melting solid (29-30 • C), soluble in water, and a weak base (pKa = 0.56) [15]. Several studies were performed and displayed a wide range of pharmacological activities for quinoxaline derivatives (Figure 1) [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Additionally, quinoxalines are used for crop protection as a component of insecticides, herbicides, and fungicides [31][32][33][34][35].…”