title: Design of potential reverse transcriptase inhibitor containing Isatin nucleus using molecular modeling studies.
abstract: Two Dimensional (2D) and Three Dimensional (3D) Quantitative Structure-Activity Relationship (QSAR) studies were performed for correlating the chemical composition of Isatin analogues and their anti-HIV activity using Multiple Linear Regression (MLR) Analysis and k Nearest Neighbor Molecular Field Analysis (kNN MFA), respectively. New Chemical Entities (NCEs) were designed using results of QSAR studies. Binding affinities of designed NCEs were studied on Reverse Transcriptase enzyme using docking studies and their ADME properties were also predicted. Finally most promising compounds were selected from molecular modeling studies. Five compounds containing Isatin nucleus were synthesized and tested for their anti-HIV activity by performing Reverse Transcriptase Assay. Three compounds showed significant Reverse Transcriptase inhibiting activity compared to standard Navirapine. Structure-Activity Relationships were also discussed bases on obtained molecular modeling and experimental data.
authors.affiliation: Department of Medicinal Chemistry, AISSMS College of Pharmacy, Near RTO, Kennedy Road, Pune 411 001, India.
authors.forename: Vidya
authors.initials: V
authors.lastname: Pawar
authors.forename: Deepak
authors.initials: D
authors.lastname: Lokwani
authors.forename: Shashikant
authors.initials: S
authors.lastname: Bhandari
authors.forename: Debashis
authors.initials: D
authors.lastname: Mitra
authors.forename: Sudeep
authors.initials: S
authors.lastname: Sabde
authors.forename: Kailash
authors.initials: K
authors.lastname: Bothara
authors.forename: Ashwini
authors.initials: A
authors.lastname: Madgulkar
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007098:Imino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007510:Isatin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015233:Models, Statistical; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000631:Aminopyridines; D007098:Imino Acids; D018894:Reverse Transcriptase Inhibitors; D007510:Isatin