New 4-[(1-benzyl-1H-indol-3-yl)carbonyl]-3-hydroxyfuran-2(5H)-ones, beta-diketo acid analogs as HIV-1 integrase inhibitors.
In addition to our recent report on a series of rationally designed benzylindolyldiketo acids acting as potent HIV-1 integrase strand transfer inhibitors, we disclose the results obtained with novel compounds chemically modified on the diketo acid moiety in order to investigate its influence on the biological activity and cytotoxicity. The activity of designed and synthesized 4-[(1-benzyl-1H-indol-3-yl)carbonyl]-3-hydroxyfuran-2(5H)-one derivatives lies in the micromolar range with regard to HIV IN enzymatic activity. The microwave-assisted synthesis was employed in some steps of the chemical procedures.
Ferro
Stefania
S
Dipartimento Farmaco-Chimico, Università di Messina, Messina, Italy. sferro@pharma.unime.it
Barreca
Maria Letizia
ML
De Luca
Laura
L
Rao
Angela
A
Monforte
Anna Maria
AM
Debyser
Zeger
Z
Witvrouw
Myriam
M
Chimirri
Alba
A
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006678:HIV / Q000187:drug effects / Q000254:growth & development; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D020128:Inhibitory Concentration 50; D007651:Keto Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000821:virology; D008872:Microwaves; D008958:Models, Molecular; D015394:Molecular Structure
D019428:HIV Integrase Inhibitors; D007211:Indoles; D007651:Keto Acids; D015107:4-Butyrolactone