Novel lavendamycin analogues as potent HIV-reverse transcriptase inhibitors: Synthesis and evaluation of anti-reverse transcriptase activity of amide and ester analogues of lavendamycin

被引:30
作者
Behforouz, M [1 ]
Cai, W
Stocksdale, MG
Lucas, JS
Jung, JY
Briere, D
Wang, AQ
Katen, KS
Behforouz, NC
机构
[1] Ball State Univ, Dept Chem, Muncie, IN 47306 USA
[2] Ball State Univ, Dept Biol, Muncie, IN 47306 USA
关键词
D O I
10.1021/jm0304414
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页码:5773 / 5780
页数:8
相关论文
共 28 条
[1]   ISOLATION OF LAVENDAMYCIN A NEW ANTIBIOTIC FROM STREPTOMYCES-LAVENDULAE [J].
BALITZ, DM ;
BUSH, JA ;
BRADNER, WT ;
DOYLE, TW ;
OHERRON, FA ;
NETTLETON, DE .
JOURNAL OF ANTIBIOTICS, 1982, 35 (03) :259-265
[2]   Chemistry of quinoline-5,8-diones [J].
Behforouz, M ;
Haddad, J ;
Cai, W ;
Gu, ZX .
JOURNAL OF ORGANIC CHEMISTRY, 1998, 63 (02) :343-346
[3]   Highly efficient and practical syntheses of lavendamycin methyl ester and related novel quinolindiones [J].
Behforouz, M ;
Haddad, J ;
Cai, W ;
Arnold, MB ;
Mohammadi, F ;
Sousa, AC ;
Horn, MA .
JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (19) :6552-6555
[4]   BETA-CARBOLINES DERIVED FROM BETA-METHYLTRYPTOPHAN AND A STEREOSELECTIVE SYNTHESIS OF 2RS,3SR)-BETA-METHYLTRYPTOPHAN METHYL-ESTER [J].
BEHFOROUZ, M ;
ZARRINMAYEH, H ;
OGLE, ME ;
RIEHLE, TJ ;
BELL, FW .
JOURNAL OF HETEROCYCLIC CHEMISTRY, 1988, 25 (06) :1627-1632
[5]   EFFECT OF 2',3'-DIDEHYDRO-3'-DEOXYTHYMIDINE IN AN IN-VITRO HOLLOW-FIBER PHARMACODYNAMIC MODEL SYSTEM CORRELATES WITH RESULTS OF DOSE-RANGING CLINICAL-STUDIES [J].
BILELLO, JA ;
BAUER, G ;
DUDLEY, MN ;
COLE, GA ;
DRUSANO, GL .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (06) :1386-1391
[6]   STREPTONIGRIN AND LAVENDAMYCIN PARTIAL STRUCTURES - PROBES FOR THE MINIMUM, POTENT PHARMACOPHORE OF STREPTONIGRIN, LAVENDAMYCIN, AND SYNTHETIC QUINOLINE-5,8-DIONES [J].
BOGER, DL ;
YASUDA, M ;
MITSCHER, LA ;
DRAKE, SD ;
KITOS, PA ;
THOMPSON, SC .
JOURNAL OF MEDICINAL CHEMISTRY, 1987, 30 (10) :1918-1928
[7]   Non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors: Past, present, and future perspectives [J].
Campiani, G ;
Ramunno, A ;
Maga, G ;
Nacci, V ;
Fattorusso, C ;
Catalanotti, B ;
Morelli, E ;
Novellino, E .
CURRENT PHARMACEUTICAL DESIGN, 2002, 8 (08) :615-657
[8]   ANTI-TUMOR ACTIVITY IN MICE OF 4'-DEOXYDOXORUBICIN IN COMPARISON WITH DOXORUBICIN [J].
CASAZZA, AM ;
SAVI, G ;
PRATESI, G ;
DIMARCO, A .
EUROPEAN JOURNAL OF CANCER & CLINICAL ONCOLOGY, 1983, 19 (03) :411-418
[9]  
CHOU J, 1987, DOSE BEFFECT ANAL MC
[10]   QUANTITATIVE-ANALYSIS OF DOSE-EFFECT RELATIONSHIPS - THE COMBINED EFFECTS OF MULTIPLE-DRUGS OR ENZYME-INHIBITORS [J].
CHOU, TC ;
TALALAY, P .
ADVANCES IN ENZYME REGULATION, 1984, 22 :27-55