title: Pharmacophoric model building for antitubercular activity of the individual Schiff bases of small combinatorial library.
abstract: Synthesis and evaluation of anti-TB activity of individual compounds of Schiff bases combinatorial library were done against Mycobacterium tuberculosis H(37)Rv at a single concentration of 6.25mug/mL according to the protocol of TAACF. Compounds 2C and 3D produced 99% inhibitory activity on the investigated organism, while the other tested compounds showed lower activity ranging from 35 to 84%. It was found that there are no relation between the anti-TB activity of the tested compounds and their lipophilicity expressed by ClogP of these compounds. A 3D pharmacophoric model has been generated by Molecular Operating Environment (MOE) using a training set of 10 reported anti-TB compounds and testing the synthesized compounds (1A, 1B, 1D, 1E, 2C, 3A, 3C, 3D, 3E and 4A-4E). The generated pharmacophoric features include, F1: hydrogen bond donors (Don), F2: aromatic rings (Aro), F3: hydrogen bond acceptors (Acc)/metal ligator (ML), F4: Aro/hydrophobic (Hyd). In all hit set, it was found that the amidic nitrogen CONH-NC fitted the region of the Don, F1, while the amidic carbonyl group fitted the region of the Acc/ML, F3. The distances bridging F1 to F2, F3 and F4 were essential for anti-TB activity in the developed pharmacophore model, as it was confirmed from model validation procedure.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
authors.forename: Wesam S
authors.initials: WS
authors.lastname: Abdel-Aal
authors.forename: Hoda Y
authors.initials: HY
authors.lastname: Hassan
authors.forename: Tarek
authors.initials: T
authors.lastname: Aboul-Fadl
authors.forename: Adel F
authors.initials: AF
authors.lastname: Youssef
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D015195:Drug Design; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D012545:Schiff Bases / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000995:Antitubercular Agents; D012545:Schiff Bases