Table 3.

Calculated binding free energy and estimated inhibition constant (K_i) of erlotinib (as control), gefitinib and quinazoline-indole hybrids 4a–h with epidermal growth factor receptor (EGFR) kinase domain.

Ligand	Hb Distance (Å)	Hb Interacting Atoms	FEB (kcal/mol)	Ic, Ki (nM)
Control (erlotinib)	2.2	Met769 O–Erl HN2	−8.71	414.12
Gefitinib	-	-	−10.74	13.34
4a	2.9 2.0	Thr766 OG1–4a HN2 Asp831 OD1–4a HN	−11.03	8.22
4b	2.1	Met769 O–4b HN	−9.95	50.7
4c	-	-	−10.10	39.74
4d	-	-	−10.31	27.74
4e	3.0	Asp831 OD1–4e HN	−11.46	4.01
4f	-	-	−9.67	81.76
4g	-	-	−10.30	28.38
4h	-	-	−10.36	25.61

Hb: Hydrogen bond; FEB: Free energy of binding; Ic: Estimated inhibition constant.