Novel lavendamycin analogues as potent HIV-reverse transcriptase inhibitors: synthesis and evaluation of anti-reverse transcriptase activity of amide and ester analogues of lavendamycin.
Novel lavendamycins including two water soluble derivatives were synthesized via short and efficient methods. Pictet-Spengler condensation of 7-N-acylamino-2-formylquinoline-5,8-diones with tryptophans produced lavendamycin esters or amides 11-17. Lavendamycins 18-21 were obtained, respectively, by further transformations of 13-15 and 17. Several lavendamycins were found to be potent HIV reverse transcriptase inhibitors with very low toxicity in vitro and in vivo. Several compounds also acted either additively or synergistically to inhibit enzyme activity together with AZT-triphosphate.
Behforouz
Mohammad
M
Chemistry and Biology Departments, Ball State University, Muncie, Indiana 47306-0440, USA.
Cai
Wen
W
Stocksdale
Mark G
MG
Lucas
Jennifer S
JS
Jung
Joo Yong
JY
Briere
Daniel
D
Wang
Aiqin
A
Katen
Kevin S
KS
Behforouz
Nancy C
NC
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D054306:Dideoxynucleotides; D004357:Drug Synergism; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013308:Streptonigrin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D013942:Thymine Nucleotides / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000577:Amides; D054306:Dideoxynucleotides; D004952:Esters; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; D013308:Streptonigrin; D015215:Zidovudine; C052873:zidovudine triphosphate; C034566:lavendamycin; D054303:HIV Reverse Transcriptase