The anti-HIV actions of 7- and 10-substituted camptothecins.
نویسندگان
چکیده
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-1(IIIB) in C8166 were 24.2, 4.2 and 198.1, and against clinical isolated strain HIV-1(KM018) 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-2(CBL-20) were 34.5, 10.7 and 317.0, respectively, and the TI of the three compounds against HIV-2(ROD) 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.
منابع مشابه
Design, Synthesis, Molecular Modeling Study and Biological Evaluation of New N'-arylidene-pyrido[2,3-d]pyrimidine-5-carbohydrazide Derivatives as Anti-HIV-1 Agents
In an attempt to identify potential new agents that are active against HIV-1, a series of novel pyridopyrimidine-5-carbohydrazide derivatives featuring a substituted benzylidene fragment were designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors. The cytotoxicity profiles of these compounds showed no significant toxicity to human cells and they exhibited anti...
متن کاملDesign, Synthesis, Molecular Modeling Study and Biological Evaluation of New N'-arylidene-pyrido[2,3-d]pyrimidine-5-carbohydrazide Derivatives as Anti-HIV-1 Agents
In an attempt to identify potential new agents that are active against HIV-1, a series of novel pyridopyrimidine-5-carbohydrazide derivatives featuring a substituted benzylidene fragment were designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors. The cytotoxicity profiles of these compounds showed no significant toxicity to human cells and they exhibited anti...
متن کاملKaolin-SO3H nanoparticles: A new efficient and reusable catalyst for synthesis of 2-substituted benzimidazoles at room temperature
Kaolinite clay found its application in medicine, in toothpaste, in cosmetic and as a food additive. Recently, a specially formulated spray is used in fruit and vegetable production to repel the insects and prevent sunburn. Kaolin-SO3H nanoparticles were prepared via reaction of kaolin and chlorosulfonic acid and characterized by FT-IR, XRD, FESEM, TEM, XRF, EDS, BET and TGA. 2-Substituted benz...
متن کاملTackling HIV in MENA: Talk Is Not Enough–It Is Time for Bold Actions: A Response to Recent Commentaries
متن کامل
Venom Components of Iranian Scorpion Hemiscorpius lepturus Inhibit the Growth and Replication of Human Immunodeficiency Virus 1 (HIV-1)
Background: During the recent years, significant progress has been achieved on development of novel anti-viral drugs. Natural products are assumed as the potential sources of novel anti-viral drugs; therefore, there are some previous studies reporting the anti-viral compounds from venomous animals. Based on the significant value for tracing of non-toxic anti-viral agents from natural resources,...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Molecules
دوره 15 1 شماره
صفحات -
تاریخ انتشار 2009