Modification at the C9 position of the marine natural product isoaaptamine and the impact on HIV-1, mycobacterial, and tumor cell activity.
作者： Waseem Gul , Nicholas L. Hammond , Muhammad Yousaf , John J. Bowling , Raymond F. Schinazi
DOI: 10.1016/J.BMC.2006.08.042
关键词:
摘要: As part of an investigation to generate optimized drug leads from marine natural pharmacophores for the treatment neoplastic and infectious diseases, a series novel isoaaptamine analogs were prepared by coupling acyl halides C9 position (2) isolated Aaptos sponge. This library new semisynthetic products was evaluated biological activity against HIV-1, Mtb, AIDS-OI, tropical parasitic cancer. Compound 4 showed potent HIV-1 (EC50 0.47 μg/mL), compound 19 proved possess remarkable Mycobacterium intracellulare with IC50 MIC value 0.15 0.31 μg/mL, while compounds 17 possessed anti-leishmanial values 0.1 0.4 respectively. Compounds 16 antimalarial EC50 230 240 ng/mL, respectively, 14 exhibited 0.05 μM Leukemia cell line K-562.
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sci-hub.se 参考文章(19)
Cynthia A. Romerdahl, Marina Moran, Jonathan George, Denise Perron, Gerhard Keilhauer, Xiao-Dong Qian, Donna Conlon, Peter F. Bousquet, Renee Miller, Kathleen M. Fitzgerald, Miguel F. Braña, Celia Cocchiaro, Preclinical evaluation of LU 79553: a novel bis-naphthalimide with potent antitumor activity. Cancer Research. ,vol. 55, pp. 1176- 1180 ,(1995)
Graham J. Atwell, Bruce F. Cain, Bruce C. Baguley, Graeme J. Finlay, William A. Denny, Potential antitumor agents. 43. Synthesis and biological activity of dibasic 9-aminoacridine-4-carboxamides, a new class of antitumor agent. Journal of Medicinal Chemistry. ,vol. 27, pp. 1481- 1485 ,(1984) , 10.1021/JM00377A017
G.J. Finlay, J.-F. Riou, B.C. Baguley, From amsacrine to DACA (N-[2-(dimethylamino)ethyl]acridine-4-carboxamide): Selectivity for topoisomerases I and II among acridine derivatives European Journal of Cancer. ,vol. 32, pp. 708- 714 ,(1996) , 10.1016/0959-8049(95)00604-4
Hideshi Nakamura, Jun'ichi Kobayashi, Yasushi Ohizumi, Yoshimasa Hirata, Isolation and structure of aaptamine a novel heteroaromatic substance possessing α-blocking activity from the sea sponge Aaptos aaptos Tetrahedron Letters. ,vol. 23, pp. 5555- 5558 ,(1982) , 10.1016/S0040-4039(00)85893-1
George R. Pettit, Holger Hoffmann, Delbert L. Herald, Peter M. Blumberg, Ernest Hamel, Jean M. Schmidt, Yung Chang, Robin K. Pettit, Nancy E. Lewin, Larry V. Pearce, Antineoplastic agents. 499. Synthesis of hystatin 2 and related 1H-benzo[de][1,6]-naphthyridinium salts from aaptamine. Journal of Medicinal Chemistry. ,vol. 47, pp. 1775- 1782 ,(2004) , 10.1021/JM030070R
George R. Pettit, Holger Hoffmann, James McNulty, Kerianne C. Higgs, Alison Murphy, David J. Molloy, Delbert L. Herald, Michael D. Williams, Robin K. Pettit, Dennis L. Doubek, John N. A. Hooper, Leslie Albright, Jean M. Schmidt, Jean-Charles Chapuis, Larry P. Tackett, Antineoplastic agents. 380. Isolation and X-ray crystal structure determination of isoaaptamine from the Republic of Singapore Hymeniacidon sp. and conversion to the phosphate prodrug hystatin 1. Journal of Natural Products. ,vol. 67, pp. 506- 509 ,(2004) , 10.1021/NP0204592
John L. Nitiss, Junfang Zhou, Angela Rose, Yuchu Hsiung, Kevin C. Gale, Neil Osheroff, The bis(naphthalimide) DMP-840 causes cytotoxicity by its action against eukaryotic topoisomerase II. Biochemistry. ,vol. 37, pp. 3078- 3085 ,(1998) , 10.1021/BI9723257
Tao Wang, Zhongxing Zhang, Owen B. Wallace, Milind Deshpande, Haiquan Fang, Zheng Yang, Lisa M. Zadjura, Donald L. Tweedie, Stella Huang, Fang Zhao, Sunanda Ranadive, Brett S. Robinson, Yi-Fei Gong, Keith Ricarrdi, Timothy P. Spicer, Carol Deminie, Ronald Rose, Hwei-Gene Heidi Wang, Wade S. Blair, Pei-Yong Shi, Pin-fang Lin, Richard J. Colonno, Nicholas A. Meanwell, Discovery of 4-benzoyl-1-[(4-methoxy-1H- pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2- (R)-methylpiperazine (BMS-378806): a novel HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions. Journal of Medicinal Chemistry. ,vol. 46, pp. 4236- 4239 ,(2003) , 10.1021/JM034082O
Ya-Ching Shen, Tain-Tsair Lin, Jyh-Horng Sheu, Chang-Yih Duh, Structures and Cytotoxicity Relationship of Isoaaptamine and Aaptamine Derivatives Journal of Natural Products. ,vol. 62, pp. 1264- 1267 ,(1999) , 10.1021/NP990156G
Rachel A Hutchins, James M Crenshaw, David E Graves, William A Denny, None, Influence of substituent modifications on DNA binding energetics of acridine-based anticancer agents. Biochemistry. ,vol. 42, pp. 13754- 13761 ,(2003) , 10.1021/BI035434W