Abstract: Camptothecin (CPT), a traditional anti-tumor drug, has been shown to possess anti-HIV-1 activity. To increase the antiviral potency, the anti-HIV activities of two CPT derivatives, 10-hydroxy-CPT and 7-hydroxymethyl-CPT, were evaluated in vitro. The therapy index (TI) of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-1IIIB in C8166 were 24.2, 4.2 and 198.1, and against clinical isolated strain HIV-1KM018 in PBMC were 10.3, 3.5 and 66.0, respectively. While the TI of CPT, 10-hydroxy-CPT and 7-hydroxymethyl-CPT against HIV-2CBL-20 were 34.5, 10.7 and 317.0, respectively, and the TI of the three compounds against HIV-2ROD showed the similar values. However, when the antiviral mechanisms were considered, we found there was no inhibition of 7-hydroxymethyl-CPT on viral cell-to-cell transmission, and was no inhibition on reverse transcriptase, protease or integrase in cell-free systems. 7-Hydroxymethyl-CPT showed no selective killing of chronically infected cells after 3 days of incubation. In conclusion, 7-hydroxymethyl-CPT showed more potent anti-HIV activity, while 10-hydroxy-CPT had less efficient activity, compared with the parent CPT. Though the antiviral mechanisms remain to be further elucidated; the modification of -OH residues at C-7 of CPT could enhance the antiviral activity, while of -OH residues at C-10 of CPT had decreased the antiviral activity, which provides the preliminary modification strategy for anti-viral activities enhancement of this compound.
Keywords: camptothecin; anti-HIV agents; HIV
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Li, Y.-Y.; Chen, S.-W.; Yang, L.-M.; Wang, R.-R.; Pang, W.; Zheng, Y.-T. The Anti-HIV Actions of 7- and 10-Substituted Camptothecins. Molecules 2010, 15, 138-148.
Li Y-Y, Chen S-W, Yang L-M, Wang R-R, Pang W, Zheng Y-T. The Anti-HIV Actions of 7- and 10-Substituted Camptothecins. Molecules. 2010; 15(1):138-148.
Li, Yu-Ye; Chen, Shi-Wu; Yang, Liu-Meng; Wang, Rui-Rui; Pang, Wei; Zheng, Yong-Tang. 2010. "The Anti-HIV Actions of 7- and 10-Substituted Camptothecins." Molecules 15, no. 1: 138-148.