تحضير مشتقات الثيازول واختبارها بيولوجياً كمضادات حيوية ضد الأورام

A series of thiazole derivatives bearing amino, acetamido or thioureido synthons at position 2- and thiosemicarbazone or 1,2,4-triazolethione moieties at position 4- have been synthesized and evaluated for their antimicrobial and antitumor activities. Some of the tested compounds (5,6,14 and 15) proved to possess ^remarkable antitumor antibiotic activity. The antimicrobial potency is found mainly to be against Gram positive bacterfa. The detailed synthesis, spectroscopic and biological data are reported.تم تخليق مجموعة من مشتقات الثيازول واختبارها كمواد لها نشاط ضد البكتريا والأورام . واشتملت هذه المركبات على تلك المشتقات التي تحمل مجاميع أمين أو أسيتاميد أو ثيويوريدو في موقع رقم 2 وكذلك التي تحمل مجاميع ثيوسيميكر بازون أو 4,2,1 - تريازول ثيون في موقع رقم 4 . وقد ثبت أن لبعض المركبات التي تم اختيارها (وهي رقم 5 , 14,6, 15 ) نشاط حيوي قوي وملحوظ ضد الأورام - وقد وجد أن تأثير هدْه المركبات كمضادة للميكروبات يكون أساساً ضد بكتريا جرام الموجبة . وتذكر هذه الدراسة تفاصيل عملية تخليق المركبات ونتائج الدراسات الاسبكتروسكوبية والبيولوجية

The in vitro antitumor assay of 5-(Z)-arylidene-4-imidazolidinones in screens of AIDS-related leukemia and lymphomas.

Thirty-one different 5-(Z)-arylidene-4-imidazolidinones were tested on six AIDS-related lymphoma (ARL) tumor cell lines, one leukemia CCRF-CEM cell culture and five different lymphoma cell lines: RL, KD-488, AS283, PA682 and SU-DHL-7. The investigated compounds showed remarkable activity against ARL, compounds 3d and 5c proved to inhibit AS283 and SU-DHL-7 cell lines, respectively, both at a GI50 value of 0.03 microM. The 2-(2-carboxyphenylamino) series proved to be the most active members in this investigation. Compounds 6b and 6d showed GI50 (MGMID) values of 6.1 and 8.7 microM, respectively, against the studied six ARL

Synthesis, biological evaluation and molecular modeling study of new (1,2,4-triazole or 1,3,4-thiadiazole)-methylthio-derivatives of quinazolin-4(3H)-one as DHFR inhibitors

A new series of 2-mercapto-quinazolin-4-one analogues was designed, synthesized and evaluated for their in vitro DHFR inhibition, antitumor and antimicrobial activity. Compound 17 proved to be the most active DHFR inhibitor with IC value of 0.01 lM, eight fold more active than methotrexate (MTX). Compounds 16 and 24 showed antitumor activity against human Caco2 colon and MCF-7 breast tumor cell lines with IC 50 50 values of 25.4 and 9.5 lg/ml, respectively. Compounds 15, 20, 21 and 30 showed considerable activity against the Gram-positive bacteria Staphylococcus aureus while 24 and 30 proved active against Bacillus subtilis with a magnitude of potency comparable to the broad spectrum antibiotic Ciprofloxacin. Strong activity was observed for 13, 14, 19, 20 and 24 against Candida albicans and Aspergillus flavus. Compound 17 shared a similar molecular docking mode with MTX and made a critical hydrogen bond and arene-arene interactions via Ala9 and Phe34 amino acid residues, respectively

Synthesis, Anticonvulsant Activity and Molecular Modeling Study of Some New Hydrazinecarbothioamide, Benzenesulfonohydrazide, and Phenacylace- tohydrazide Analogues of 4(3H)-quinazolinone

A new series of quinazoline analogues was designed and synthesized to get the target compounds 18- 21, 30-41, 46-53, and 57-76. The Obtained compounds were evaluated for their anticonvulsant activity using PTZ and picrotoxin convulsive models. Compounds 47, 63, 68 and 73 proved to be the most active compounds in this study with a remarkable 100% protection against PTZ induced convulsions. Compounds 47, 63, 68 and 73 proved to be 10, 4, 4, and 5 fold more active, respectively than the used positive control sodium valproate. Structure activity correlation concluded valuable pharmacophoric information which confirmed by molecular modeling studies. Molecular docking study of 68 suggested its agonistic behavior toward GABAA receptor. The studied quinazoline analogues could be considered as useful templates for future development and further derivatization

Synthesis, biological evaluation and molecular modeling study of some new thiazolodiazepine analogs as CNS active agents

New derivatives of ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124, 3), were synthesized as continuation to our previous patented efforts. Compounds 15 and 20 showed marginal hypnotic potency compared to 3. Compounds 15 (0.78 mmol/kg) and 20 (0.39 mmol/kg) showed remarkable 100% protection against PTZ induced convulsions with two and four fold increase in activity than sodium valproate (1.38 mmol/kg), respectively. Molecular modeling studies showed hydrogen bonding interaction between 15 and Thr56 residues at the binding site of GABA . Superposition, flexible alignment and surface mapping of 15, 20 and diazepam supports their biological resemblance where ADMET study suggested that those compounds could be used as oral anticonvulsants