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Synthesis, anticancer, anti-HIV-1, and antimicrobial activity of some tricyclic triazino and triazolo[4,3-e]purine derivatives

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Abstract

In an effort to etablish new candidates with improved antineoplastic, anti-HIV-1 and antimicrobial activities, the synthesis of some new triazino and triazolo[4,3-e]purine derivatives is described: 6,8-dimethyl-1,4-dihydro-1,2,4-triazino[4,3-e]purine-7,9(6H, 8H)-diones 3–6; 5,7,9-trimethyl-1,2,4-triazolo[4,3-e]purine-6,8(5H, 7H, 9H)-diones 11–13, together with the synthesis of the 8-substituted purine derivative: 8-(3,5-diamino-1H-pyrazol-4-yl)diazenyl-1,3-dimethyl-1H-purine-2,6(3H, 7H)-dione 7. The prepared compounds were tested for their in vitro anticancer, anti-HIV and antimicrobial activities. The results of the in vitro anticancer screening revealed that compound 3 exhibited considerable activity against melanoma MALME-3 M, non-small lung cancer HOP-92 and breast cancer T-47D (GI50 values of 25.2, 31.8, and 32.9 μM, respectively). The anti-HIV-1 results indicated that compounds 7 and 13c displayed moderate activity (maximum % cell protection 30.52 and 35.54 at 2 × 10−4 M, respectively). The in vitro antimicrobial data showed that compound 12 was the most active against P. aeruginosa, it was equipotent to ampicillin (MIC < 100 μg/ml). While compound 11d was the most active against P. vulgaris, it was as active as ampicillin (MIC < 50 μg/ml). In addition, compounds 12 and 13c were the most active against S. aureus (MIC <50 and <25 μg/ml, respectively). On the other hand, the tested compounds devoid of antifungal activity except 6b and 11c which showed weak activity against A. niger.

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Acknowledgments

The authors with to thank Dr. Manal A. Shalaby, Genetic Engineering and Biotechnology Research Institute (GEBRI), Mubark City for Scientific Research and Technology Application, Borg El-Arab, Alexandria, Egypt for performing the antibacterial and antifungal screening. The authors are also grateful to the staff of the Department of Health and Human Services, National Cancer Institute, Bethesda, Maryland, USA for the anti-cancer and anti-HIV reports.

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  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria, AR, Egypt

    Fawzia A. Ashour, Samia M. Rida, Soad A. M. El-Hawash, Mona M. ElSemary & Mona H. Badr

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  1. Fawzia A. Ashour
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  2. Samia M. Rida
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  3. Soad A. M. El-Hawash
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Correspondence to Fawzia A. Ashour.

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Ashour, F.A., Rida, S.M., El-Hawash, S.A.M. et al. Synthesis, anticancer, anti-HIV-1, and antimicrobial activity of some tricyclic triazino and triazolo[4,3-e]purine derivatives. Med Chem Res 21, 1107–1119 (2012). https://doi.org/10.1007/s00044-011-9612-6

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