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

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 (GI 50 values of 25.2, 31.8, and 32.9 lM, 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 9 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 lg/ml). While compound 11d was the most active against P. vulgaris, it was as active as ampicillin (MIC \ 50 lg/ml). In addition, compounds 12 and 13c were the most active against S. aureus (MIC \50 and \25 lg/ml, respectively). On the other hand, the tested compounds devoid of antifungal activity except 6b and 11c which showed weak activity against A. niger.

Synthesis, spectral analysis, molecular docking and DFT studies of 3-(2, 6-dichlorophenyl)-acrylamide and its dimer through QTAIM approach

“…Ashour et al. were reported C=C stretching vibrations of aromatic heterocyclic ring usually observe at 1576 and 1568 cm −1 [ 28 ]. In titled compound the C=C bond appeared at 1427 and 1549 cm −1 in FT-IR spectrum and their PED calculation gives stretching frequency at 1572 and 1644 cm −1 .…”

“…In dimer, for N-O observed stretching frequency has good agreement with theoretical value. Ashour et al were reported C¼C stretching vibrations of aromatic heterocyclic ring usually observe at 1576 and 1568 cm À1 [28]. In titled compound the C¼C bond 1 2 3…”

Synthesis of some novel purine derivatives incorporating tetrazole ring and investigation of their antimicrobial activity and DNA interactions

“…Several adenine derivatives have been reported for antimicrobial agent (Ashour et al, 2012;Hirokawa et al, 2009;Proszenyak et al, 2007;Tunçbilek et al, 2009). Additionally, these antimicrobial agents are more effective when compared to our adenine derivatives.…”

“…Purine analogues have gained much attention in the last few decades and become an important topic in medicine and biology. Several purine analogues, which have antitubercular, antiulcer, antimicrobial, antifungal, antineoplastic, antitumor, antiviral and cardiotonic properties, have been reported (Beena and Rawat, 2013;Park et al, 2011;Qu et al, 2008;Galmarini et al, 2002;Lambert et al, 1990;Jacobson et al, 2012;Bonan et al, 2000;Tunçbilek et al, 2009;Ashour et al, 2012).…”

Design, Molecular Modeling and Synthesis of Some New Purine-diones and Pyridopyrimidine-diones with Anticancer Activity

“…Several of the latter heterocycles possess a multitude of pronounced biological activities 8 . These derivatives have been utilized extensively in medicinal chemistry due to their privileged structure that show various pharmacological activities, such as, anticancer [9][10][11][12][13][14][15] , anti-inflammatory [16][17][18][19][20] , anticonvulsant [21][22][23] and antibacterial 12,18,[24][25][26] and antidiabetic activities through inhibition of phosphoenolpyruvate carboxykinase (PEPCK) 27, 28 among others. Moreover, recently 1,8-disubstituted purine-2,6-diones [AH-216 (II), AH-217 (III); chart 2] were reported to possess potent antitumor activity against breast cancer and leukemia 10 .…”