1-(5-Bromo-4-phenyl-1,3-thia­zol-2-yl)pyrrolidin-2-one

The asymmetric unit of the title compound, C13H11BrN2OS, consists of two crystallographically independent mol­ecules (A and B). In each mol­ecule, the pyrrolidine ring adopts an envelope conformation with a methyl­ene C atom as the flap atom. In mol­ecule A, the central thia­zole ring makes a dihedral angle of 36.69 (11)° with the adjacent phenyl ring, whereas the corresponding angle is 36.85 (12)° in mol­ecule B. The pyrrolidine ring is slightly twisted from the thia­zole ring, with C—N—C—N torsion angles of 4.8 (3) and 3.0 (4)° in mol­ecules A and B, respectively. In the crystal, C—H⋯π and π–π [centroid-to-centroid distance = 3.7539 (14) Å] inter­actions are observed. The crystal studied was a pseudo-merohedral twin with twin law (-100 0-10 101) and a refined component ratio of 0.7188 (5):0.2812 (5)

S-Phenyl 4-meth­oxy­benzothio­ate

In the mol­ecule of the title thio­ester, C14H12O2S, the dihedral angle between the phenyl and benzene rings is 71.8 (3)°. The meth­oxy group is essentially coplanar with the benezene ring to which it is bonded, with an r.m.s. deviation of 0.0065 (5) Å for the non-H atoms involved. In the crystal, weak C—H⋯π inter­actions are present

DNA binding of ethyl 2-substituted aminothiazole-4-carboxylate analogues: A molecular modeling approach to predict their antitumor activity

The synthesis and the antitumor potential of 2-substituted aminothiazole-4-carboxylate, structurally-related to the antitumor antibiotic netropsin (NT) were reported. However, the exact mode of action and SAR of these compounds remained undefined. Currently, an energy-based molecular modeling approach has been utilized to highlight the mode of interaction of these compounds with β-DNA and characterize the structural requirements of biologically active aminothiazoles. Employing netropsin (NT) as a template and nine different 2-aminothiazole analogues have been examined for their capacity to interact with the DNA structure based on the number and pattern of H-bonding, energy of binding, conformational changes of compounds due to docking, and the width change of DNA minor groove. Positive correlation (R2 = 0.94) was found between (Ebinding) of the used 2-aminothiazoles and their antitumor activity, thus substantiating the utility of this modeling approach in future design of similar compounds

N-substituted-piperidines as Novel Anti-alzheimer Agents: Synthesis, antioxidant activity, and molecular docking study

Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining carbamoylpiperidine analogs containing nipecotic acid scaffold were described. Then, a series of hybrids have been developed by introducing Free radical scavengers. Molecular modeling was performed and structure activity relationships are discussed. Among the series, most potent compounds showed effective AchE inhibitions, high selectivity over butyrylcholinesterase and high radical scavenging activities. On the basis of this work, the ability of analogs containing nipecotic acid scaffold to serve in the design of N-benzyl-piperidine linked multipotent molecules for the treatment of Alzheimer Disease. Keywords: Synthesis, N-substituted-piperidines, Antioxidant activity, ATP chemiluminescence, Molecular modeling stud

Synthesis and Biological Evaluation of Some New Thiazolodiazepine Analogues as CNS Active Agents

PhDThe ultra‐short ac ng ac vity of ethyl 8‐oxo‐5,6,7,8‐tetrahydro‐thiazolo[3,2‐a] [1,3]diazepin‐3‐carboxylate (HIE‐124, 12), as a member of a novel class, which might overcome many of the disadvantages and problems that usually associated the use of thiopental or benzodiazepines as intravenous anesthetic agents has been reported. The present investigation is directed toward the synthesis of new derivatives of the parent thiazolo[3,2‐a][1,3]diazepine (HIE‐124, 12), in continuation to the previous patented efforts in this area. These derivatives possess the potential to exhibit a promising and varying range of CNS activities, including, among others, hypnotic and anticonvulsant activities. The proposed compounds were synthesized according to the designed strategy. Structure elucidation of the synthesized intermediates and final products was attained by the aid of IR, 1H, 13C NMR, and mass spectrometry. The synthesized compounds were evaluated for various CNS activities. The new analogues Ethyl 3‐methyl‐8‐oxo‐5,6,7,8‐tetrahydro‐thiazolo[3,2‐a] [1,3]diazepine‐2‐carboxylate (35) and 2‐Bromo‐3‐methyl‐6,7‐dihydro‐thiazolo[3,2‐a] [1,3]diazepin‐8(5H)‐one (40) showed marginal hypnotic potency compared to what was reported about the parent compound HIE‐124 (12). Biological screening results allowed the allocation of two potent anticonvulsant agents worth patency. Compounds 35 and 40 proved to be the most active compounds in the present inves ga on as an convulsants with remarkable 100% protec on against PTZ induced convulsions as compared with the standard drug valproic acid. It is worth mentioning that compounds 35 (0.78 mmole/kg) and 40 (0.39 mmole/kg) proved to be almost two and four fold more ac ve, respec vely; than the used posi ve control sodium valproate (1.38 mmole/kg). Structure activity correlation of the obtained results revealed that, CNS activity is embedded in the structure core (8‐oxo‐5,6,7,8‐tetrahydro‐thiazolo[3,2‐a][1,3]diazepine) of the investigated compounds. Structure activity relationships (SAR) were deduced from the obtained data. These studied 8‐oxo‐5,6,7,8‐tetrahydro‐thiazolo[3,2‐a][1,3]diazepine analogues could be considered as useful templates for future development and further derivatization or modification to obtain more potent CNS active compounds

Substituted thiazoles VI. Synthesis and antitumor activity of new 2-acetamido- and 2 or 3-propanamido- thiazole analogs

A novel series of 2-acetamido and 2 or 3-propanamido derivatives of 4- or 5- substituted-thiazoles was designed and synthesized. Structure elucidation of the new synthesized compounds was attained by the use of C NMR, and Mass spectrometry. Compounds were subjected to NCI in vitro assessment for their antitumor activity, at a single dose of 10 μM of test compounds. Compounds bearing straight chain substituent or 4-phenyl function proved to be more active than their branched or 4-methyl congeners. Compounds 37, 41 and 42 exhibited broad spectrum antitumor activity. Compounds 23 and 27 proved lethal while compounds 18, 21, 32 and 37 showed remarkable GI values of 75.5, 69.3, 96.2 and 92.7% to the Leukemia CCRF-CEM cell line, respectively

Derivatives of Cucurbitacin-E-glucoside produced by Curvularia lunata NRRL 2178: Anti-inflammatory, antipyretic, antitumor activities, and effect on biochemical parameters

Cucurbitacin E glucoside (1) is a tetracyclic triterpenoid glucoside, isolated from Cucurbitaceae plants. In the present study the pharmacological and biochemical effects of cucurbitacin-E-glucoside and two of its microbial transformation derivatives (2 and 3) produced by Curvularia lunata NRRL 2178, were investigated. The isolated compounds were identified by 1H and 13C NMR spectroscopy. The obtained results showed that 2 and 3 possess anti-inflammatory and antipyretic effects, compared with indomethacin and acetaminophen. Oral administration of 2 and 3 at dose of 1/10 of LD50 for 30 days resulted in a significant decrease in the serum levels of glucose, cholesterol and triacylglycerol. Cucurbitacin–E-glucoside showed moderate cytotoxicity against tumor cell lines while compound 3 proved to be selective against colon carcinoma cell lines

Interaction of some new 2-(substituted-thio)-quinazolin-4-ones with molybdenum hydroxylases: A pharmacophore prediction

Background: Molybdenum hydroxylases have been implicated as key oxidative enzymes in some diseases. Methods: Twenty 2-(substituted-thio)-quinazolin-4-one derivatives recently synthesized in our laboratory were examined for their inhibitory activity toward molybdenum hydroxylases. Results and conclusion: The tested quinazolines inhibited both xanthine oxidase and aldehyde oxidase enzymes in a competitive pattern with Ki values range of 66–753 μM. Pharmacophore prediction methodology was used to study the structure requirements of those inhibitors

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