Tuberculosis caused by Mycobacterium tuberculosis, is one of the most infectious diseases at present world. The WHO has reported that 14 million people worldwide are infected with active tuberculosis and over 1.7 million deaths occur every year. There are many drugs available in the market for treating tuberculosis, but the emergence of tuberculosis is due to the appearance of Multi Drug Resistance (MDR) against one or more of the 1st line antimycobacterial drug. Therefore, there is a need to explore and develop newer structural moiety as antitubercular drug. In the present study, 2D and 3D QSAR analysis of a series of 2, 3- substituted quinazolin-4(3H)-one was performed using vLife MDS software package, version 3.5. Various statistically significant models were obtained, from which the most robust model for 2D QSAR with r2 = 0.82, q2 = 0.67, F test = 41, pred_r2 =0.65 values and for 3D QSAR with r2 = 0.93, q2 = 0.90, F test = 45, pred_r2 =0.52 values were obtained. In 2D QSAR, distance based topological like SssOcount and alignment independent topological descriptors such as T_C_N_2, T_O_O_2, T_O_Cl_7 showed significant correlation for antitubercular activity. In 3D QSAR study the positive steric contribution indicates that the bulker group is essential for enhanced biological activity while the negative electronic parameter highlights that an electronegative substitution is essential at 2 and 3-position of quinazolinone ring. The positive contribution of electronic parameter at 6th position reveals that the bromine atom shall be replaced with hydrogen and iodine to obtain molecules with better activity. The results obtained from 2D and 3D QSAR studies provide useful substitution patterns on the quinazolinone skeleton which may be helpful for the designing of more potent antitubercular agents.
