Anticonvulsant Classes and Possible Mechanism of Actions.

Epilepsy is considered one of the most common neurological disorders worldwide; it needs long-term or life-long treatment. Despite the presence of several novel antiepileptic drugs, approximately 30% patients still suffer from drug-resistant epilepsy. Subsequently, searching for new anticonvulsants with lower toxicity and better efficacy is still in paramount demand.

Microwave-assisted synthesis of novel steroidal heterocyclic analogs as potent inhibitors of RANKL-induced osteoclastogenesis.

Osteoporosis is a significant public health issue in our aging population. It is an excessive bone resorption condition brought on by osteoclastogenesis, which makes bones more brittle. In the present work, a series of novel heterosteroidal derivatives have been synthesized using the microwave technique and were evaluated as antiosteoclastogenic agents.

Exploring new cyclohexane carboxamides based GABA agonist: Design, synthesis, biological evaluation, in silico ADME and docking studies.

The new series of 5a-e, 6a-e and 7a-e derivatives were designed, synthesized and tested for their anticonvulsant activity using "gold standard methods" ScPTZ and MES model, neurotoxicity, liver enzymes and neurochemical assay. Screening of the synthesized analogues exhibited variable anticonvulsant potential especially in chemically induced seizures. Quantification study showed that compounds 6d and 6e were the most potent analogues with ED 44.

Design and synthesis of some barbituric and 1,3-dimethylbarbituric acid derivatives: A non-classical scaffold for potential PARP1 inhibitors.

Six series based on barbituric acid 5a-e, 10a-d; thiobarbituric acid 6a-e, 11a-d and 1,3-dimethylbarbituric acid 7a-e, 12a-d were prepared and screened for their in vitro PARP1 inhibition. They revealed promising inhibition at nanomolar level especially compounds 5c, 7b, 7d and 7e (IC = 30.51, 41.

Discovery of novel urea-diarylpyrazole hybrids as dual COX-2/sEH inhibitors with improved anti-inflammatory activity and highly reduced cardiovascular risks.

Herein we describe our efforts to develop novel anti-inflammatory/analgesic agents devoid of known cardiovascular drawbacks. In doing so, two 1,5-diarylpyrazole series of urea linked (9a-f) and amide linked (11a-f) compounds were synthesized and evaluated in vitro as dual COX-2/sEH inhibitors using recombinant enzyme assays. The in vivo anti-inflammatory and analgesic activities were then examined using reported animal models.

Design, synthesis and docking studies of novel benzopyrone derivatives as anticonvulsants.

A series of coumarin derivatives 6-8, 9a-h, 11 and 13a, b -16a, b was synthesized and screened for their anticonvulsant profile. Screening of these analogues using the 'gold standard methods' revealed variable anticonvulsant potential with remarkable effects observed particularly in chemically-induced seizure test. Compounds 6, 7, 13b disclosed the highest potency among the series with 100% protection against scPTZ.

Design and synthesis of novel PARP-1 inhibitors based on pyridopyridazinone scaffold.

Various pyridopyridazinone derivatives were designed as Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. The pyridopyridazinone scaffold was used as an isostere of the phthalazine nucleus of the lead compound Olaparib in addition to some modifications in the tail part of the molecule. Preliminary biological evaluation indicated that most compounds possessed inhibitory potencies comparable to Olaparib in nanomolar level.

Screening and optimization of samarium-assisted complexation for the determination of norfloxacin, levofloxacin and lomefloxacin in their corresponding dosage forms employing spectrofluorimetry.

Multivariate strategy was applied for setting a fluorescent technique for the determination of three fluoroquinolones: norfloxacin (NOR), levofloxacin (LEV) and lomefloxacin (LOM) in their pure powder and dosage forms. Based on their known interaction with lanthanides, and augmented fluorescence intensity obtained by antenna effect at λ/λ = 314/553, 312/553 and 310/556 for NOR, LEV and LOM, respectively, the current research was scrutinized. Four continuous factors were selected for study in the screening step by means of Plackett-Burman Design, where temperature factor was excluded for being non-significant and the other factors as volume of metal ion solution, pH and reaction time were evaluated through Central Composite Design.

Design and synthesis of novel 5-(4-chlorophenyl)furan derivatives with inhibitory activity on tubulin polymerization.

Aim: Discovery of novel series of colchicine binding site inhibitors (CBSIs).

Materials & Methods: Isoxazoline 3a-d, pyrazoline 4a-b, 7a-f and 8a-f, cyclohexenone 9a-b and 10a-b or pyridine derivatives 11a-b were synthesized and evaluated for their inhibition of tubulin polymerization and cytotoxicity. Most of the compounds displayed potent to moderate antitumor activity against leukemia SR cell line.

Design, synthesis and biological evaluation of some novel quinazolinone derivatives as potent apoptotic inducers.

Aim: Novel quinazolinone and triazinoquinazolinone derivatives were designed and synthesized as apoptotic inducers.

Methodology/results: Most of the synthesized compounds showed excellent antiproliferative activity against MCF-7 and HCT-116 cell lines, respectively. Compounds 7a, 8a, 8d, 14a and 14d were superior to doxorubicin as activators of caspases 3, 8 and 9 in HCT-116 cell line.

Novel diphenylthiazole derivatives with multi-target mechanism: Synthesis, docking study, anticancer and anti-inflammatory activities.

Over the last few decades, a growing body of studies addressed the anticancer activity of NSAIDs, particularly selective COX-2 inhibitors. However, their exact molecular mechanism is still unclear and is not fully investigated. In this regard, a novel series of compounds bearing a COXs privilege scaffold, diphenyl thiazole, was synthesized and evaluated for their anticancer activity against a panel of cancer cell lines.

Design, synthesis and analgesic/anti-inflammatory evaluation of novel diarylthiazole and diarylimidazole derivatives towards selective COX-1 inhibitors with better gastric profile.

The inhibition of gastric cyclooxygenase 1 (COX-1) enzyme was believed to be the major cause of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric ulcer. Recent studies disproved this belief and showed that the gastric tissues vulnerability is not solely connected to COX-1 inhibition. This work aimed at exploring and rationalizing the differential analgesic and anti-inflammatory activities of novel selective COX-1 inhibitors with improved gastric profile.

Design, synthesis and molecular docking of novel diarylcyclohexenone and diarylindazole derivatives as tubulin polymerization inhibitors.

New target compounds were designed as inhibitors of tubulin polymerization relying on using two types of ring B models (cyclohexenone and indazole) to replace the central ring in colchicine. Different functional groups (R) were attached to manipulate their physicochemical properties and/or their biological activity. The designed compounds were assessed for their antitumor activity on HCT-116 and MCF-7 cancer cell lines.

Novel pyrazolopyrimidine derivatives targeting COXs and iNOS enzymes; design, synthesis and biological evaluation as potential anti-inflammatory agents.

A novel set of 4-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidine and 5-substituted-1-phenyl-pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and evaluated as potential anti-inflammatory agents. The newly prepared compounds were assessed through the examination of their in vitro inhibition of four targets; cyclooxygenases subtypes (COX-1 and COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-κB). Compounds 8a, 10c and 13c were the most potent and selective ligands against COX-2 with inhibition percentages of 79.

Simultaneous determination of chlordiazepoxide and selected antidepressants using CZE.

A simple CE method was developed and validated for the simultaneous determination of chlordiazepoxide (CHL), amitriptyline, and nortriptyline (mixture I) or the determination of CHL and imipramine (mixture II) using the same BGE. Sertraline and amitriptyline were used as internal standards for the first and second mixtures, respectively. The method allows amitriptyline to be completely separated from its impurity and main metabolite nortriptyline, which can be quantified from 0.

3-{[5-(4-Chloro-phen-yl)-3-methyl-1H-pyrazol-1-yl]meth-yl}-4-m-tolyl-1H-1,2,4-triazole-5(4H)-thione.

In the title compound, C20H18ClN5S, the toluene and triazole rings are oriented almost perpendicular to each other, making a dihedral angle of 89.97 (9)°, whereas the dihedral angle between cholorophenyl and pyrazole rings is 54.57 (11)°.

4-[5-(4-Chloro-phen-yl)-3-methyl-1H-pyrazol-1-yl]benzene-sulfonamide.

In the title compound, C(16)H(14)ClN(3)O(2)S, the dihedral angle between the benzene and pyrazole rings is 52.75 (2)°, while that between the pyrazole and 4-chloro-phenyl rings is 54.0 (3)°.

Design, Synthesis and Biological Evaluation of Novel Pyrimido[4,5-d]pyrimidine CDK2 Inhibitors as Anti-Tumor Agents.

A series of 2,5,7-trisubstituted pyrimido[4,5-d]pyrimidine cyclin-dependent kinase (CDK2) inhibitors is designed and synthesized. 6-Amino-2-thiouracil is reacted with an aldehyde and thiourea to prepare the pyrimido[4,5-d]-pyrimidines. Alkylation and amination of the latter ones give different amino derivatives.