Design, synthesis, and and biological evaluation of triazolopyrimidine hybrids as multitarget directed anticancer agents.

In response to the urgent need for new anti-proliferative agents, four novel series of triazolopyrimidine compounds (7a-e, 9a-d, 11a-f, and 13a-e) were synthesized and evaluated for anticancer efficacy against HCT116, HeLa, and MCF-7 cell lines. Compound 13c emerged as the most potent, with IC values of 6.10, 10.

Exploration of antiproliferative potential of modified triazole-benzohydrazone scaffold: Multitarget approach.

A novel series of triazole-benzohydrazone hybrids was efficiently designed and synthesized as antiproliferative agents, targeting different kinases. All compounds were screened via the National Cancer Institute (NCI) against 60 cancer cell lines, where compounds 16, 17, and 18 exhibited growth inhibition percent (GI%) of various leukemia subpanels with values of 70.33%, 64.

Nitroimidazole derivatives potentiated against tumor hypoxia: Design, synthesis, antitumor activity, molecular docking study, and QSAR study.

A hypoxic environment occurs predominantly in tumors. During the growth phase of a tumor, it grows until it exceeds its blood supply, leaving regions of the tumor in which the oxygen pressure is dramatically low. They are virtually absent in normal tissues, thus creating perfect conditions for selective bioreductive therapy of tumors.

Modified Tacrine Derivatives as Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Synthesis, Biological Evaluation, and Molecular Modeling Study.

To develop multitarget-directed ligands (MTDLs) as potential treatments for Alzheimer's disease (AD) and to shed light on the effect of the chromene group in designing these ligands, 35 new tacrine-chromene derivatives were designed, synthesized, and biologically evaluated. Compounds and exhibited the most desirable multiple functions for AD; they were strong AChE inhibitors with IC values of 0.44 and 0.

Synthesis, Antitumor Activity, and Drug Design of New Thieno[2,3-]Pyrimidine-4-One Derivatives as Nonclassical Lipophilic Dihydrofolate Reductase Inhibitors.

Synthesis of a new series of 20 compounds bearing the thieno[2,3-]pyrimidine-4-one scaffold was achieved. The inhibitory activity of these compounds was performed over 60 cell lines of human tumor at single and five dose concentrations. Compounds , , and exhibited potent growth inhibitions toward the majority of the tested NCI 60 cell lines.

Insights into modulating the monastrol scaffold: Development of new pyrimidinones as Eg5 inhibitors with anticancer activity.

Based on modulation of the monastrol scaffold, two series of pyrimidinone derivatives, 3a-e and 5a-k, were designed, synthesized, and investigated for their in vitro anticancer activity. Compound 5j exhibited the most potent cytotoxic activity against four cancer cell lines, including HCT-116, HeLa, HEPG-2, and MCF-7, with IC values of 3.75-5.

Design, synthesis, and analysis of antiproliferative and apoptosis-inducing activities of nitrile derivatives containing a benzofuran scaffold: EGFR inhibition assay and molecular modelling study.

New cyanobenzofurans derivatives were synthesised, and their antiproliferative activity was examined compared to doxorubicin and Afatinib (IC = 4.17-8.87 and 5.

Design, synthesis and molecular modeling of phenyl dihydropyridazinone derivatives as B-Raf inhibitors with anticancer activity.

Three new series of phenyl dihydropyridazinone derivatives 4b-8i have been designed, synthesized and evaluated for their anticancer activity against different cancer cell lines. Nine compounds showed strong inhibitory activity, among which compound 8b exhibited potent activity against PC-3 cell line with IC value of 7.83 µM in comparison to sorafenib (IC 11.

1,2,3-Triazole-Chalcone hybrids: Synthesis, in vitro cytotoxic activity and mechanistic investigation of apoptosis induction in multiple myeloma RPMI-8226.

A new series of 1,2,3-triazole-chalcone hybrids has been synthesized and screened in vitro against a panel of 60 human cancer cell lines according to NCI (USA) protocol. Compound 4d having 3, 4-dimethoxyphenyl chalcone moiety, the most potent derivative, inhibited the growth of RPMI-8226 and SR leukemia cell lines by 99.73% and 94.

Design, Synthesis and Anticancer Evaluation of New Substituted Thiophene-Quinoline Derivatives.

A series of new isoxazolyl, triazolyl and phenyl based 3-thiophen-2-yl-quinoline derivatives were synthesized adopting click chemistry approach. In addition, the synthesis of new useful synthon, (2-chloroquinolin-3-yl) (thiophen-2-yl) methanol, is reported. The obtained compounds were characterized by spectral data analysis and evaluated for their anticancer activity.

Identification of 1-pyrazolo[3,4-b]pyridine derivatives as potent ALK-L1196M inhibitors.

Anaplastic lymphoma kinase (ALK) has been recognised as a promising molecular target of targeted therapy for NSCLC. We performed SAR study of pyrazolo[3,4-b]pyridines to override crizotinib resistance caused by ALK-L1196M mutation and identified a novel and potent L1196M inhibitor, . displayed exceptional enzymatic activities (<0.

Dihydrofolate reductase inhibition effect of 5-substituted pyrido[2,3-d]pyrimidines: Synthesis, antitumor activity and molecular modeling study.

A new series of pyrido[2,3-d]pyrimidines 3-18 bearing substitution at C-5 position was synthesized. All compounds were tested for their in vitro antitumor activity against five human cancer cell lines namely; hepatocellular carcinoma (HePG2), breast carcinoma (MCF-7), human prostate carcinoma (PC3), colorectal carcinoma (HCT-116), and cervical carcinoma (Hela) using doxorubicin as a positive control. Compounds 3, 4, 9, 11, 13, 14, 15 and 17 exhibited the highest antitumor activity against the tested cell lines and were selected to screen their enzymatic inhibition against dihydrofolate reductase enzyme (DHFR) compared with the reference drug methotrexate (MTX), to explain the probable mechanism of action of the observed anticancer activity.

Design, synthesis and docking study of novel picolinamide derivatives as anticancer agents and VEGFR-2 inhibitors.

Two series of picolinamide derivatives bearing (thio)urea and dithiocarbamate moieties were designed and synthesized as VEGFR-2 kinase inhibitors. All the new compounds were screened for their cytotoxic activity against A549 cancer cell line and VEGFR-2 inhibitory activity. Compounds 7h, 9a and 9l showed potent inhibitory activity against VEGFR-2 kinase with IC values of 87, 27 and 94 nM, respectively in comparison to sorafenib (IC = 180 nM) as a reference.

Synthesis and anticancer activity of new dihydropyrimidinone derivatives.

A series of dihydropyrimidinone derivatives bearing various N-heterocyclic moieties was designed and synthesized. Twelve new compounds were screened for their cytotoxic activity using 60 cancer cell lines according to NCI (USA) protocol. Compound 19 showed a significant activity against NCI-H460, SK-MEL-5, and HL-60 (TB) cell lines with growth inhibition 88%, 86% and 85%, respectively, and was found to be more safe on normal cells when compared to doxorubicin.

Design, synthesis, and molecular modeling of heterocyclic bioisostere as potent PDE4 inhibitors.

A new hybrid template was designed by combining the structural features of phosphodiesterase 4 (PDE4) inhibitors with several heterocyclic moieties which present an integral part in the skeleton of many apoptotic agents. Thirteen compounds of the synthesized hybrids displayed higher inhibitory activity against PDE4B than the reference drug, roflumilast. Further investigation indicated that compounds 13b and 20 arrested the cell cycle at the G2/M phase and the pre-G1 phase, and induced cell death by apoptosis of A549 cells in a caspase-dependent manner.

Enantioselective ruthenium-catalyzed 1,3-dipolar cycloadditions between C-carboalkoxy ketonitrones and methacrolein: solvent effect on reaction selectivity and its rational.

A catalytic 1,3-dipolar cycloaddition between carboalkoxy ketonitrones and methacrolein under the effect of chiral ruthenium Lewis acid (R,R-1) was developed with high regio-, diastereo-, and enantiocontrol. The diastereochemical outcome of the cycloaddition reaction is marked by a significant solvent effect, and a divergent endo or exo control can be tuned by an appropriate choice of both the solvent and the N- and O-substituents of the ketonitrone. A rationale of the solvent effect, based on the computational study of the interactions between the methacrolein-Ru complex and its counteranion (SbF6(-)), is proposed to explain the selectivities obtained.

Chiral N-heterocyclic carbene-copper(I)-catalyzed asymmetric allylic arylation of aliphatic allylic bromides: steric and electronic effects on γ-selectivity.

Chiral N-heterocyclic carbene ligands were electronically and sterically tuned to improve γ-selectivity in copper(I)-catalyzed asymmetric allylic arylation of aliphatic allylic bromides with several aryl Grignard reagents. High γ-selectivity was realized when either the aryl group of the Grignard reagent or the aryl group on the N-substituent of the carbene ligand was electron-deficient or when either the carbene ligand or allylic bromide was bulky. The results indicated that electron deficiency and steric hindrance of the initially formed σ-allyl copper intermediate enhance the rate of the reductive elimination to give γ-products as major isomers.

Copper-catalyzed asymmetric allylic substitution with aryl and ethyl Grignard reagents.

Phenyl- and ethyl-magnesium bromides undergo regioselective asymmetric allylic substitution with high enantioselectivity under the catalysis of chiral amidophosphane-copper(I) complexes.