Design and synthesis of caffeoyl-anilides as portmanteau inhibitors of HIV-1 integrase and CCR5

Hardik S Bodiwala; Sudeep Sabde; Pawan Gupta; Ruchira Mukherjee; Rajender Kumar; Prabha Garg; Kamlesh Kumar Bhutani; Debashis Mitra; Inder Pal Singh

doi:10.1016/j.bmc.2010.12.031

Design and synthesis of caffeoyl-anilides as portmanteau inhibitors of HIV-1 integrase and CCR5

Bioorg Med Chem. 2011 Feb 1;19(3):1256-63. doi: 10.1016/j.bmc.2010.12.031. Epub 2010 Dec 21.

Authors

Hardik S Bodiwala¹, Sudeep Sabde, Pawan Gupta, Ruchira Mukherjee, Rajender Kumar, Prabha Garg, Kamlesh Kumar Bhutani, Debashis Mitra, Inder Pal Singh

Affiliation

¹ Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160 062, India.

PMID: 21227704
DOI: 10.1016/j.bmc.2010.12.031

Abstract

Designing multi-functional ligands is a recent strategy by which multiple targets can be inhibited by a single entity. A series of caffeoyl-anilide compounds based on structures of various integrase and CCR-5 inhibitors have been designed and synthesized as anti-HIV agents in the present study. Most of the compounds exhibited potent anti-HIV activity at micromolar concentration in CEM-GFP CD4+ T cells infected with HIV-1NL4.3 virus. Compound 14 showed a lower EC(50) and better TI as compared to AZT. Mechanism based studies suggest that these compounds inhibit either one or in some cases, both the targets. The experimental data and the docking results showed that these compounds are potential inhibitors for both HIV-1 IN and CCR5.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetanilides / chemical synthesis*
Acetanilides / chemistry
Acetanilides / pharmacology*
Anilides / analysis
Anilides / chemical synthesis*
Anilides / pharmacology
Anti-HIV Agents / chemical synthesis*
Anti-HIV Agents / chemistry
Anti-HIV Agents / pharmacology*
CCR5 Receptor Antagonists*
Caffeic Acids / chemical synthesis*
Caffeic Acids / chemistry
Caffeic Acids / pharmacology*
Drug Design
HIV Integrase Inhibitors / chemical synthesis*
HIV Integrase Inhibitors / chemistry
HIV Integrase Inhibitors / pharmacology*
HIV-1 / drug effects*
HIV-1 / physiology
Ligands
Models, Molecular
Molecular Structure
Structure-Activity Relationship
Virus Replication / drug effects

Substances

Acetanilides
Anilides
Anti-HIV Agents
CCR5 Receptor Antagonists
Caffeic Acids
HIV Integrase Inhibitors
Ligands
N-(4-(3-(3,4-dihydroxyphenyl)acryloyl)phenyl)-2-(thiophen-2-yl)acetamide