Browsing by Author "Eissa I.H."

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    Design, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents
    (Elsevier B.V., 2017) El-Helby A.G.A.; Ayyad R.R.; Sakr H.M.; Abdelrahim A.S.; El-Adl K.; Sherbiny F.S.; Eissa I.H.; Khalifa M.M.; Pharmaceutical Chemistry Department; Faculty of Pharmacy (Boys); Al-Azhar University; Cairo; 11884; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy; Delta University for Science and Technology; Gamasa; Dakahlia; Egypt; Organic Chemistry Department; Faculty of Pharmacy; Al-Azhar University (Boys); Cairo; 11884; Egypt; Organic Chemistry Department; Faculty of Pharmacy; October University for Modern Science and Arts (MSA); 6th October City; 11787; Egypt
    In view of their expected anticonvulsant activity, some novel derivatives of 2,3-dihydrophthalazine-1,4-dione 4�22 were designed, synthesized and evaluated using pentylenetetrazole (PTZ) and picrotoxin as convulsion-inducing models. Moreover, the most active compounds were tested against electrical induced convulsion using maximal electroshock (MES) models of seizures. Most of the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 13 and 14g were proved to be the most potent compounds of this series with relatively low toxicity in the median lethal dose test when compared with the reference drug. Molecular modeling studies were done to verify the biological activity. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogues. 2016 Elsevier B.V.
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    Synthesis, characterization and molecular docking studies of thiouracil derivatives as potent thymidylate synthase inhibitors and potential anticancer agents
    (Springer International Publishing, 2017) El-Naggar A.M.; Abou-El-Regal M.M.; El-Metwally S.A.; Sherbiny F.F.; Eissa I.H.; Chemistry Department; Faculty of Science; Ain Shams University; Abbassia; Cairo; 11566; Egypt; Higher Technology Institute; 10th of Ramadan City; Egypt; Organic Chemistry Department; Faculty of Pharmacy (Boys); Al-Azhar University; Cairo; 11884; Egypt; Organic Chemistry Department; Faculty of Pharmacy; October University for Modern Science and Arts (MSA); 6th October City; 11787; Egypt; Pharmaceutical Chemistry Department; Faculty of Pharmacy (Boys); Al-Azhar University; Cairo; 11884; Egypt
    Thymidylate synthase (TS), one of folate-dependent enzymes, is a key and well-recognized target for anticancer agents. In this study, a series of 6-aryl-5-cyano thiouracil derivatives were designed and synthesized in accordance with essential pharmacophoric features of known TS inhibitors. Nineteen compounds were screened in vitro for their anti-proliferative activities toward HePG-2, MCF-7, HCT-116, and PC-3 cell lines. Compounds 21c, 21d, and 24 exhibited high anti-proliferative activity, comparable to that of 5-fluorouracil. Additionally, ten compounds with potent anti-proliferative activities were further evaluated for their ability to inhibit TS enzyme. Six compounds (21b, 21c, 21d, 22, 23 and 24) demonstrated potent dose-related TS inhibition with IC 50 values ranging from 1.57 to 3.89?M. The in vitro TS activity results were consistent with those of the cytotoxicity assay where the most potent anti-proliferative compounds of the series showed good TS inhibitory activity comparable to that of 5-fluorouracil. Furthermore, molecular docking studies were carried out to investigate the binding pattern of the designed compounds with the prospective target, TS (PDB-code: 1JU6). � 2017, Springer International Publishing AG.