November-December 2019 Indian Journal of Pharmaceutical Sciences 1078 Research Paper *Address for correspondence E-mail: sushilkashaw@gmail.com Accepted 11 October 2019 Revised 13 July 2019 Received 09 March 2019 Indian J Pharm Sci 2019;81(6):1078-1088 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms QSAR, Pharmacophore Mapping and Molecular Docking of 2,4-Diaminoquinazoline as Antitubercular Scaffold: A Computational Hybrid Approach PRIYANKA BOSE, MITALI MISHRA, ASMITA GAJBHIYE AND S. K. KASHAW* Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar-470 003, India Bose et al.: 2,4-Diaminoquinazoline as Antitubercular Scaffold: A Computational Hybrid Approach The 2,4-diaminoquinazoline is a well-known scaffold with a great potential to generate a library. In the following research work different computational strategies were applied on 2,4-diaminoquinazoline moiety to estimate its effciency as an antitubercular scaffold among its other versatile biological activities reported in several published studies. Each data has defned specifc substitution mode on the scaffold to be active on different protein site or for disease condition. The following experiment regards of 2D-QSAR, 3D-QSAR, active site and blind docking, structural orientation, pharmacophore mapping and further designing of the data set with possible real active moiety. 2D-QSAR has shown good reliability with r 2 = 0.8190, q 2 _LOO = 0.7711 and external pred_r 2 = 0.5321, along with 3D-QSAR has good predictability, q 2 (r 2 cv) = 0.7601, pred_r 2 = 0.5567. Further ligand based pharmacophore mapping was carried out for estimating atomic contribution to chemical feature for the compound. The generated hypothesis established that hydrogen accepter, donor and aromatic ring with electronegative atom are the important features. Finally, outcomes of all results were recapitulated to design new compounds. Some compounds also were designed depending on the computational fnding and concludes the suitability of the scaffold to be antiTB active. Key words: Computational strategy, QSAR, docking, pharmacophore mapping, molecular designing, antiTB activity, validation With the increase in the statistics of the tuberculosis (TB) affected population and the multiplicity of the types and symptoms of TB each year, a scary picture has emerged in the worldwide scenario. In 2016, 4.1 % of new cases and 19 % cases of multidrug resistant or rifampicin-resistant TB have been listed in the report [1,2] . After the resistance to isoniazid, resistance to other frst line drugs is also emerging with time reducing treatment and maintenance options for TB patients. In this context, a new versatile molecular structure is the requirement for generating new leads and fnally for a drug molecule development. Among different well known scaffolds, 2,4-diaminoquinazoline has been an attractive system and reported to be effective against Mycobacterium tuberculosis in a promising way [3] . The diaminoquinazoline pharmacophore is a versatile moiety, as smallest changes in the functional subgroup surprisingly revealed new novel potential compounds on a number of protein family. The moiety with different group substitution have drawn much attention due to their wide range of biological activities for example, antimalarial [4,5] , antileshmanial [6] , antipsychotic [7] , antitubercular, anticancer drugs [8,9] . The concept of being the scaffold to be antiTB template was frst found in 2000 over a public data service system [10] . In 2008 in an US patent, it was frst described that the modifcation over the quinazoline ring system specifcally at 2,4 position on the quinazoline ring as well as the benzene ring can be exploited to develop potent antiTB drug candidate [11,12] . With that goal more