title: Design and synthesis of caffeoyl-anilides as portmanteau inhibitors of HIV-1 integrase and CCR5.
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.
authors.affiliation: Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar, Punjab 160 062, India.
authors.forename: Hardik S
authors.initials: HS
authors.lastname: Bodiwala
authors.forename: Sudeep
authors.initials: S
authors.lastname: Sabde
authors.forename: Pawan
authors.initials: P
authors.lastname: Gupta
authors.forename: Ruchira
authors.initials: R
authors.lastname: Mukherjee
authors.forename: Rajender
authors.initials: R
authors.lastname: Kumar
authors.forename: Prabha
authors.initials: P
authors.lastname: Garg
authors.forename: Kamlesh Kumar
authors.initials: KK
authors.lastname: Bhutani
authors.forename: Debashis
authors.initials: D
authors.lastname: Mitra
authors.forename: Inder Pal
authors.initials: IP
authors.lastname: Singh
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000813:Anilides / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D002109:Caffeic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000083:Acetanilides; D000813:Anilides; D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D002109:Caffeic Acids; D019428:HIV Integrase Inhibitors; D008024:Ligands; C560455:N-(4-(3-(3,4-dihydroxyphenyl)acryloyl)phenyl)-2-(thiophen-2-yl)acetamide