Design and synthesis of new nicotinamides as immunomodulatory VEGFR-2 inhibitors and apoptosis inducers.

Nicotinamide-based VEGFR-2 inhibitors have good contribution in drug discovery. Development of novel nicotinamides as VEGFR-2 inhibitors. different and assays were conducted to evaluate the VEGFR-2 inhibition and cytotoxicity.

Discovery of New Immunomodulatory Anticancer Thalidomide Analogs: Design, Synthesis, Biological Evaluation and In Silico Studies.

New thalidomide analogs have been designed and synthesized by hybridizing the immunomodulatory gutarimide moiety with three antiproliferative nuclei: quinazolinedione, phthalazinedione, and quinoxalinone. The biological results revealed the strong impact of quinazoline derivatives 7 a and 28, and phthalazine based 20 a against HepG-2, MCF-7, PC3, and HCT-116 cell lines, compared to thalidomide. In particular, compound 20 a was the most promising as it had far better biological activity than thalidomide with regard to inhibition of TNF-α, IL-6, caspase 3, COX-I/II, and VEGFR-2, as well as cell cycle arrest, and apoptosis rate enhancement in MCF-7 cells, the most sensitive cell line to the current new molecules.

New immunomodulatory anticancer quinazolinone-based thalidomide analogs: design, synthesis and biological evaluation.

The current work is an extension to our previous work for the development of new thalidomide analogs. Quinazolinone-based molecules carrying a glutarimide moiety have been designed, synthesized and biologically evaluated for immunomodulatory and anticancer activity. Compounds and showed considerable immunomodulatory properties in comparison to thalidomide.

New nicotinamide derivatives as potential anticancer agents targeting VEGFR-2: design, synthesis, , and studies.

Herin, new nicotinamide candidates were designed and synthesized as VEGFR-2 inhibitors. antiproliferative activities were assessed against MCF-7, HepG-2 and HCT-116 cancer cell lines. The top cytotoxic members , , , and were estimated against their selected target (VEGFR-2).

Design, Synthesis, and Biological Evaluation of New Potential Unusual Modified Anticancer Immunomodulators for Possible Non-Teratogenic Quinazoline-Based Thalidomide Analogs.

Sixteen new thalidomide analogs were synthesized. The new candidates showed potent in vitro antiproliferative activities against three human cancer cell lines, namely hepatocellular carcinoma (HepG-2), prostate cancer (PC3), and breast cancer (MCF-7). It was found that compounds XII, XIIIa, XIIIb, XIIIc, XIIId, XIVa, XIVb, and XIVc showed IC values ranging from 2.

Design, synthesis, studies, and biological evaluation of novel pyrimidine-5-carbonitrile derivatives as potential anti-proliferative agents, VEGFR-2 inhibitors and apoptotic inducers.

A novel series of pyrimidine-5-carbonitrile derivatives bearing benzylidene and hydrazone moieties with different linkers (spacers) were designed and synthesized as possible inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The newly synthesized compounds were evaluated for their cytotoxic activities against two human cancer cell lines namely colon cancer (HCT-116) and breast cancer (MCF-7) using sorafenib as a standard anticancer drug. Compounds 9d, 11e, 12b, and 12d showed higher cytotoxic activities than sorafenib with IC values ranging from 1.

Novel promising benzoxazole/benzothiazole-derived immunomodulatory agents: Design, synthesis, anticancer evaluation, and in silico ADMET analysis.

Eleven novel benzoxazole/benzothiazole-based thalidomide analogs were designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against HepG-2, HCT-116, PC3, and MCF-7 cells. Generally, the open analogs with semicarbazide and thiosemicarbazide moieties (10, 13a-c, 14, and 17a,b) exhibited higher cytotoxic activities than derivatives with closed glutarimide moiety (8a-d).

Design, synthesis, anticancer evaluation, and ADMET analysis of novel thalidomide analogs as promising immunomodulatory agents.

Immunomodulatory medications like thalidomide and its analogs prevent the production of some proinflammatory cytokines linked to cancer. A new series of thalidomide analogs were designed and synthesized in order to develop potential antitumor immunomodulatory agents. The antiproliferative activities of the new candidates against a panel of three human cancer cell lines (HepG-2, PC3 and MCF-7) were assessed in comparison to thalidomide as a positive control.

Design, synthesis, anticancer evaluation, docking and ADMET analysis of novel indole-based thalidomide analogs as promising immunomodulatory agents.

In the present work, novel 16 indole-based thalidomide analogs were designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against HepG-2, HCT-116, PC3 and MCF-7 cell lines. Generally, the opened analogs of glutarimide ring exhibited higher activities than the closed ones.

Design, synthesis, and biological evaluation of novel bioactive thalidomide analogs as anticancer immunomodulatory agents.

Cancer is still a dangerous disease with a high mortality rate all over the world. In our attempt to develop potential anticancer candidates, new quinazoline and phthalazine based compounds were designed and synthesized. The new derivatives were built in line with the pharmacophoric features of thalidomide.

Discovery of New VEGFR-2 Inhibitors: Design, Synthesis, Anti-Proliferative Evaluation, Docking, and MD Simulation Studies.

Four new nicotinamide-based derivatives were designed as antiangiogenic VEGFR-2 inhibitors. The congeners were synthesized possessing the pharmacophoric essential features to bind correctly with the VEGFR-2 active pocket. All members were evaluated for their cytotoxic and VEGFR-2 inhibitory potentialities.

Design, Synthesis, Molecular Modeling and Anti-Hyperglycemic Evaluation of Quinazoline-Sulfonylurea Hybrids as Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) and Sulfonylurea Receptor (SUR) Agonists.

New quinazoline-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds VI-6-a, V, IV-4, VI-4-c, IV-6, VI-2-a, IV-1, and IV-2 were more potent than the reference glibenclamide. They induced significant reduction in the blood glucose levels of diabetic rats: 78.

New quinoline and isatin derivatives as apoptotic VEGFR-2 inhibitors: design, synthesis, anti-proliferative activity, docking, ADMET, toxicity, and MD simulation studies.

New quinoline and isatin derivatives having the main characteristics of VEGFR-2 inhibitors was synthesised. The antiproliferative effects of these compounds were estimated against A549, Caco-2, HepG2, and MDA-MB-231. Compounds and showed comparable activities with doxorubicin against the Caco-2 cells.

Synthesis, biological evaluation, and molecular docking of new series of antitumor and apoptosis inducers designed as VEGFR-2 inhibitors.

Based on quinazoline, quinoxaline, and nitrobenzene scaffolds and on pharmacophoric features of VEGFR-2 inhibitors, 17 novel compounds were designed and synthesised. VEGFR-2 IC values ranged from 60.00 to 123.

Design, synthesis and molecular modeling of new quinazolin-4(3H)-one based VEGFR-2 kinase inhibitors for potential anticancer evaluation.

Globally cancer is the second leading cause of death. So that this work is an attempt to develop new effective anti-cancer agents. In line with pharmacophoric features of VEGFR-2 kinase inhibitors, new nineteen quinazolin-4-one derivatives were designed, synthesized and biologically evaluated for their potential anticancer activity.

Discovery of new pyrimidine-5-carbonitrile derivatives as anticancer agents targeting EGFR and EGFR.

A new series of pyrimidine-5-carbonitrile derivatives has been designed as ATP mimicking tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR). These compounds were synthesized and evaluated for their in vitro cytotoxic activities against a panel of four human tumor cell lines, namely colorectal carcinoma (HCT-116), hepatocellular carcinoma (HepG-2), breast cancer (MCF-7), and non-small cell lung cancer cells (A549). Five of the synthesized compounds, 11a, 11b, 12b, 15b and 16a, were found to exhibit moderate antiproliferative activity against the tested cell lines and were more active than the EGFR inhibitor erlotinib.

Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents.

Thalidomide and its analogs are immunomodulatory drugs that inhibit the production of certain inflammatory mediators associated with cancer. In the present work, a new series of thalidomide analogs was designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against a panel of four cancer cell lines (HepG-2, HCT-116, PC3 and MCF-7).

Design, synthesis, molecular modeling and anti-hyperglycemic evaluation of phthalimide-sulfonylurea hybrids as PPARγ and SUR agonists.

New series of phthalimide-sulfonylurea hybrids were prepared and examined for their in vivo anti-hyperglycemic activities in STZ-induced hyperglycemic rats using glibenclamide as a reference drug. Compounds 6, 6, 6, 6, 6 and 6 induced significant reduction in the blood glucose levels of diabetic rats ranging from 24.43 to 21.

Synthesis, physiochemical properties, photochemical probe, and antimicrobial effects of novel norfloxacin analogues.

The emerging resistance to antimicrobial drugs demands the synthesis of new remedies for microbial infections. Attempts have been made to prepare new compounds by modifications in the quinolone structure. An important method for the synthesis of new quinolone is using Vilsmeier approach but has its own limitations.

N-Methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) and N-Methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) produce non-identical discriminative stimuli in rats.

N-Methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (methylenedioxymethamphetamine, MDMA, Ecstasy) and its structurally abbreviated congener N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA) are chemically related designer drugs, and PMMA is sometimes sold on the clandestine market as a substitute for MDMA. Prior drug discrimination studies have found that MDMA and PMMA substitute for one another suggesting that they produce similar discriminative stimulus effects in rats. However, there also are some indications that the two agents produce distinct stimulus effects.

6-(2-Phenylethyl)nicotine: a novel nicotinic cholinergic receptor ligand.

6-(2-Phenylethyl)nicotine (1b; K(i)=15 nM) was unexpectedly found to bind at alpha4beta2 nicotinic cholinergic (nACh) receptors. Although this compound failed to produce nicotine-like agonist action in several functional assays, 1b antagonized the antinociceptive effects of nicotine (mouse tail-flick assay) in a dose-dependent fashion when administered via an intrathecal route.

(-)6-n-Propylnicotine antagonizes the antinociceptive effects of (-)nicotine.

Several 6-alkyl analogues of nicotine were examined in radioligand binding and in vivo functional assays. Although (-)6-ethylnicotine (3) binds with high affinity at nACh receptors (Ki=5.6 nM) and produces nicotine-like actions, its n-propyl homologue (-)4 (Ki=22 nM) failed to produce such effects.