Alaa A. El-Tombary

Synthesis of thiazolo[4,5-d]pyrimidine derivatives as potential antimicrobial agents.

In this study, we report the synthesis and antimicrobial evaluation of several new thiazolo[4,5-d] pyrimidine derivatives, namely 7-substituted amino-5-methyl-3-phenylthiazolo[4,5-d]pyrimi-dine-2 (3H)-thiones4a- e,8,13,15, ethyl 2-cyano-2-(7-substituted-5-methyl-3-phenylthiazolo [4,5-d]-pyrimidin-2(3H)-ylidene)acetates5a- b, 2-(7-substituted-5-methyl-3-phenylthiazolo[4,5-d] pyrimidin-2(3H)-ylidene)malononitriles6a- b, 5-methyl-7-morpholino-3-phenylthiazolo[4,5-d] pyrimidine-2(3H)-one 7, and 7-[4-(1-substituted-5-phenyl-4,5-dihydro-1H-pyrazolin-3-yl)anilino]-5-methyl-3-phenylthiazolo[4,5-d]pyrimidine-2(3H)-thiones10- 12. Some of the tested compounds were more active againstC. albicans thanE. coli andP. aeruginosa, and all were inactive against S.aureus.

Synthesis of some substituted furan-2(5H)-ones and derived quinoxalinones as potential anti-microbial and anti-cancer agents

In search for novel anti-cancer and anti-microbial agents with promising pharmacotoxicological profile, the synthesis of some substituted 4-halofuran-2(5H)-ones (8a–l, 9, 11) and derived halogenated quinoxalin-2(1H)-ones (12a–d) is described. Some of the halogenated furanones were readily oxidized to the corresponding 2-bromo-2-propenoic acids (13a–c) with hydrogen peroxide in alkaline medium. Twenty-two compounds were preliminary tested for their in vitro activity against three bacteria and one fungus and revealed encouraging activity. On the other hand, three compounds were screened as anti-cancer agents using cell line panel protocol and 22 compounds were subjected to cycline-dependent kinases (CDKs) inhibition screening program but were inactive.

Synthesis and biological evaluation of novel series of thieno[2,3-d]pyrimidine derivatives as anticancer and antimicrobial agents

The present study is concerned with the synthesis, anticancer and antimicrobial screening of several new 3-substituted or 2,3-disubstituted-5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6-carboxamide derivatives. Three compounds (4b, 8c, and 11b) were selected by the National Cancer Institute and were first evaluated at a single-dose primary anticancer assay against 60 human cancer cell lines for their in vitro anticancer activity. Compound 8c which passed the criteria for activity in this assay was evaluated against the full panel of 60 human cancer cell lines at five concentrations at tenfold dilutions where it showed non-selective broad-spectrum activity against all cancer cell lines. Furthermore, compounds 4b, 6, 8c, 8d, and 16 showed pronounced antibacterial activities comparable to ampicillin against P. aeruginosa. Therefore, it was concluded that compound 8c may serve as a useful lead compound in search for powerful dual anticancer-antimicrobial agents.

Synthesis, Anti-Inflammatory, and Ulcerogenicity Studies of Novel Substituted and Fused Pyrazolo[3,4-d]pyrimidin-4-ones.

In the present investigation, some new pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives (7–12) as well as fused pyrazolo[3′,4′:4,5]pyrimido[1,2-b]pyridazin-4(1H)-one (14–16) and 7,8,9,10-tetrahydropyrazolo[3′,4′:4,5]pyrimido[1,2-b]-cinnolin-4(1H)-one (17) ring systems were synthesized using the starting compound 5-amino-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (5). The structures of the newly synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, mass spectroscopy, and elemental analysis. The theoretical calculation of their lipophilicity as C log P was performed. The anti-inflammatory activity of all newly synthesized compounds was evaluated using the carrageenan-induced paw edema test in rats using indomethacin as the reference drug. Ulcer indices for the most active compounds were calculated. Seven compounds (10b, 11a–f) showed consistently good anti-inflammatory activity. In particular, 5-{[4-(4-bromophenyl)-3-(4-chlorophenyl)-1,3-thiazol-2(3H)-ylidene]amino}-6-methyl-1-phenyl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (11e) and its 3,4-bis(4-chlorophenyl) analog (11f) were found to be the most effective among the other derivatives, showing activity comparable to that of indomethacin with minimal ulcerogenic effects. Correlation of the biological data of the active compounds with their theoretically calculated C log P values revealed that lipophilicity influences the biological response.

Synthesis and biological evaluation of some novel 2-(pyrimidin-4-yl)estradiol derivatives

Summary The preparation and characterization of some novel 2-(pyrimidin-4-yl)estradiol derivatives are presented. The synthesis was achieved by the reaction of 2-benzoylacetylestradiol 17β-acetate with guanidines, urea, thiourea and a variety of thiourea derivatives according to the Traube synthesis. The synthesized compounds were evaluated for their uterotrophic and antifertility activities in mature female albino rats. All compounds showed relatively moderate uterotrophic activity (55–73%) based on dry uterine weight gain. The antifertility activity, as assessed by the post-coital antiimplantation activity test, was also of moderate potency for most compounds. However, 2-(1- p -bromophenyl-2(1 H )-thioxo-6-phenylpyrimidin-4-yl)estradiol 8 displayed excellent antiimplantation activity (100%), and was equipotent to estradiol as an antifertility agent; 8 prevented implantation completely in rats at a dose of 0.035 mg/kg body weight.

Synthesis and Biological Evaluation of Some Novel Thieno[2,3-d] pyrimidine Derivatives as Potential Anti-inflammatory and Analgesic Agents

A novel series of thienopyrimidine derivatives bearing various substituents or linked to various heterocyclic moieties through atoms spacers were prepared starting from 5-methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidine-6- carboxamide potassium salt 3. Twelve out of the prepared compounds were selected and evaluated for their antiinflammatory activity using the formalin-induced paw edema and the turpentine oil-induced granuloma pouch bioassays using diclofenac sodium as a reference standard. The ulcerogenic effects and acute toxicity (ALD50) values of these compounds were also determined. In addition, the analgesic activity of the same compounds was evaluated using the rat tail withdrawal technique. The results revealed that compounds 5a, 13, 14b, 15a, 16a and 16b had high anti-inflammatory effect comparable to diclofenac sodium, whereas compounds 5a, 14a, 15a and 16a revealed pronounced analgesic activity that is equal or higher than that of the reference. All of the tested compounds revealed high GI safety profile and were well tolerated by the experimental animals with high safety margin (ALD50 > 3.0g/Kg).

Purines and triazolo[4,3-e]purines containing pyrazole moiety as potential anticancer and antioxidant agents

AIM Targeting apoptosis regulators such as caspases aiming at inducing apoptosis is an attractive strategy in cancer therapy. MATERIALS & METHODS 8-substituted purine incorporating pyrazole moiety were designed, synthesized and evaluated for their anticancer and antioxidant activities. RESULTS Compounds 7a and 8a displayed potent and selective anticancer activity against lung cancer A549 cell line with low cytotoxicity on peripheral blood mononuclear normal cells. Compounds 7a and 8a induced caspase dependent apoptotic death and DNA damage in all cancer cell lines. In addition, compounds 2, 5, 6a, 7a, 8a, 8c, 11a, 11b and 12b showed good antioxidant activity higher than that of the standard ascorbic acid. CONCLUSION Compounds 7a and 8a can be considered promising dual anticancer and antioxidant leads inducing caspase-dependent apoptotic death and DNA damage.