title: Molecular docking studies on tetrahydroimidazo-[4,5,1-jk][1,4]-benzodiazepinone (TIBO) derivatives as HIV-1 NNRT inhibitors.
abstract: At present, chemotherapy seems to be the main weapon in the arsenal of remedies for the ongoing crusade against AIDS. The mode of binding of the TIBO family of inhibitors has been of interest because these compounds do not fit the two-hinged-ring model as generally observed in the NNRTIs. Flexible docking simulations were performed with a series of 53 TIBO derivatives as NNRTIs. Binding preferences as well as the structural and energetic factors associated with them were studied. A good correlation (r(2)=0.849, q(2)=0.843) was observed between the biological activity and binding affinity of the compounds which suggest that the identified binding conformations of these inhibitors are reliable. Further screening of PubChem database yielded novel scaffolds. Our studies suggest that modifications to the TIBO group of inhibitors might enhance their binding efficacy and hence, potentially, their therapeutic utility.
authors.affiliation: Department of Applied Chemistry, Shri GS Institute of Technology and Sciences, 3/6 Manoramaganj, Indore 452001, MP, India. sukusap@yahoo.com
authors.forename: Nitin S
authors.initials: NS
authors.lastname: Sapre
authors.forename: Swagata
authors.initials: S
authors.lastname: Gupta
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Pancholi
authors.forename: Neelima
authors.initials: N
authors.lastname: Sapre
mesh_terms: D001569:Benzodiazepines / Q000737:chemistry* / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D016571:Neural Networks, Computer; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology
chemical_list: C476867:4,5,6,7-tetrahydroimidazo-(4,5,1- jk)(1,4)benzodiazepin-2 (1 H)-one; D007093:Imidazoles; D018894:Reverse Transcriptase Inhibitors; D001569:Benzodiazepines; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase