Design of potential reverse transcriptase inhibitor containing Isatin nucleus using molecular modeling studies.
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.
Pawar
Vidya
V
Department of Medicinal Chemistry, AISSMS College of Pharmacy, Near RTO, Kennedy Road, Pune 411 001, India.
Lokwani
Deepak
D
Bhandari
Shashikant
S
Mitra
Debashis
D
Sabde
Sudeep
S
Bothara
Kailash
K
Madgulkar
Ashwini
A
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
D000631:Aminopyridines; D007098:Imino Acids; D018894:Reverse Transcriptase Inhibitors; D007510:Isatin