Anti-HIV Activities of Precisely Defined, Semirigid, Carboxylated Alternating Copolymers

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• 作者：Alice M. Savage ; Yi Li ; Lindsay E. Matolyak ; Gustavo F. Doncel ; S. Richard Turner ; Richard D. Gandour
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：August 14, 2014
• 年：2014
• 卷：57
• 期：15
• 页码：6354-6363
• 全文大小：350K
• ISSN：1520-4804

文摘

Di-tert-butyl (E)-4,4鈥?stilbenedicarboxylate and tert-butyl 4-vinylbenzoate were copolymerized with maleic anhydride and tert-butyl 4-maleimidobenzoate, individually and respectively. After conversion into polyanions, these four copolymers exhibited activity against four HIV-1 strains: IIIb, BaL, JR-CSF, and 92UG037. For both the IIIb and BaL HIV-1 strains, the lowest IC<sub>50sub> (0.095 and 0.23 渭g/mL, respectively) values were obtained with poly(4,4鈥?stilbenedicarboxylate-alt-maleic acid) (DCSti-alt-MA). For JR-CSF and 92UG037, both tier 2 clinical isolates but different clades, DCSti-alt-MA exhibited the lowest IC<sub>50sub> (0.76 and 0.75 渭g/mL, respectively). Although DCSti-alt-MA had the lowest IC<sub>50sub> in 渭g/mL for each strain, the other copolymers had IC<sub>50sub>s less than 2-fold higher. Further, these copolymers achieved high selectivity indices (>100) for these clinical isolates. Polymer rigidity, as measured by the statistical segment length, emerged as a key property when comparing anti-HIV activities with those of other polyanions. A speculative illustration was proposed for possible modes of inhibition.