Design, Synthesis, and Cytotoxic Evaluation of Certain 7-Chloro-4-(piperazin-1-yl)quinoline Derivatives as VEGFR-II Inhibitors.

Signaling pathway inhibition of VEGFR-II is visualized as valuable tool in cancer management. In the current study, the synthesis of novel 1-4-(7-chloroquinolin-4-yl)piperazin-1-yl)-2-(N-substituted-amino)-ethanone derivatives (4a-t) was achieved through the amination of 2-chloro-1-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)ethanone (3) with different secondary amines. The structures of the target compounds were confirmed by IR, 1 H-NMR, 13 C-NMR, HRMS, and microanalysis. Compounds 4a-t were subjected to in vitro anticancer screening against human breast cancer (MCF-7) and prostate cancer (PC3) cell lines. The highest cytotoxicty against both cell lines was displayed by 2-(4-(4-bromobenzyl)piperazin-1-yl)-1-(4-(7-chloroquinolin-4-yl)piperazin-1-yl)ethanone (4q), with IC50 values of 6.502 and 11.751 µM against MCF-7 and PC3 cells, respectively, compared with the standard drug doxorubicin (MCF-7: 6.774 µM, PC3: 7.7316 µM). Due to its notable activity toward MCF-7 cells, 4q was further evaluated as VEGFR-II inhibitor, showing an IC50 of 1.38 µM compared to sorafenib (0.33 µM). The docking study proved that 4q has a binding mode akin to that of VEGFR-II inhibitors.

Synthesis, molecular modeling, and biological evaluation of novel benzimidazole derivatives as inhibitors of hepatitis C virus RNA replication.

In this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC50/90 of 4d=0.123/0.321, 4f=0.145/0.345, 4h=0.129/0.432, VX-950=0.20/0.45 µM, respectively) and 6d (IC50/90=0.116/0.452 µM) displayed activity very similar to that of the standard. Compounds 4d, 4f, 4h, and 6d were potent HCV RNA replication inhibitors and are good drug candidates for further investigations.

Pyrazolone derivatives: synthesis, anti-inflammatory, analgesic, quantitative structure-activity relationship and in vitro studies.

Some 1-(4-chlorophenyl or benzenesulfonamide)-2,3- and/or 4-substituted-1H-pyrazol-5(4H)-one derivatives were synthesized and screened for their anti-inflammatory and analgesic activities, in addition to their ulcerogenic liability. They were found to be active as anti-inflammatory and analgesic agents. Compound 6b was found to be the most active as anti-inflammatory agent and compound 9b was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, cyclooxygenase-1/-2 (COX-1)/COX-2 isozyme selectivity was also done and the tested compounds showed equal inhibition to both isoforms. Moreover, 2D-quantitative structure-activity relationship (QSAR) studies revealed well predictive and statistically significant and cross validated QSAR model that helps to explore some expectedly potent compounds.

Synthesis and anticonvulsant activity of certain substituted furochromone, benzofuran and flavone derivatives.

Synthesis of furochromone, 2-phenylchromone (flavone) and benzofuran derivatives substituted with thiosemicarbazide or thiazolidin-4-one moieties were accomplished. All the newly synthesized compounds were tested for their anticonvulsant activity in both subcutaneous pentylenetetrazole induced seizures (scPTZ) and maximal electric shock induced seizures (MES) tests using valproic acid and phenytoin respectively as reference standards. The most active compounds in scPTZ model were 1c, 2b, 5a and 7e showing 100% protection at 300 mg/kg upon intraperitoneal administration. Also, the effect of pre-treatment of three of the most active compounds (1c, 2b, 5a) on 4-amino pyridine-induced lethality in mice was investigated. Pre-treatment with these compounds significantly increased the latency for clonic and tonic seizures and prevented 4-amino pyridine induced death. Hence, this provides evidence for anticonvulsant activity of these compounds, and a neuroprotective activity for them. The structure-activity relationship was studied based on the obtained data.