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

摘要

In an effort to etablish new candidates with improved antineoplastic, anti-HIV-1 and antimicrobial activities, the synthesis of some new triazino and triazol-o[4,3-e]purine derivatives is described: 6,8-dimethyl-l, 4-dihydro-l ,2,4-triazino[4,3-e]purine-7,9(6H, 8H)-diones 3-6; 5,7,9-trimethyl-l,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-lH-pyrazol-4-yl)diazenyl-l,3-dimethyl-lH-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 uM, 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 x 10~4 M, respectively). The in vitro antimicrobial data showed that compound 12 was the most active against P. aerugin-osa, it was equipotent to ampicillin (MIC < 100 ug/ml). While compound lid was the most active against P. vul-garis, it was as active as ampicillin (MIC < 50 u.g/ml). In addition, compounds 12 and 13c were the most active against S. aureus (MIC <50 and <25 |ig/ml, respectively). On the other hand, the tested compounds devoid of antifungal activity except 6b and lie which showed weak activity against A. niger.