Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity.

Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold.

Anti-tyrosinase, anti-cholinesterase and cytotoxic activities of extracts and phytochemicals from the Tunisian Citharexylum spinosum L.: Molecular docking and SAR analysis.

Previously phytochemical investigations carried out on the flowers and trunk bark extracts of Citharexylum spinosum L. tree, allowed the isolation of twenty molecules belonging to several families of natural substances [triterpene acids, iridoid glycosides, phenylethanoid glycosides, 8,3'-neolignan glycosides, together with other phenolic compounds]. In the present work, a biological evaluation (anti-tyrosinase, anticholinesterase and cytotoxic activities) was performed on the prepared extracts and the isolated secondary metabolites.

Synthesis and Biological Screening of New Lawson Derivatives as Selective Substrate-Based Inhibitors of Cytochrome bo Ubiquinol Oxidase from Escherichia coli.

The respiratory chain of Escherichia coli contains two different types of terminal oxidase that are differentially regulated as a response to changing environmental conditions. These oxidoreductases catalyze the reduction of molecular oxygen to water and contribute to the proton motive force. The cytochrome bo oxidase (cyt bo ) acts as the primary terminal oxidase under atmospheric oxygen levels, whereas the bd-type oxidase is most abundant under microaerobic conditions.

Synthesis, biological evaluation and molecular docking analysis of novel benzopyrimidinone derivatives as potential anti-tyrosinase agents.

2-substitued-benzopyrimidinones 2 were synthesized in high to excellent yields in a single step via condensation of 2-aminobenzamide 1 with some aryl-aldehydes in the presence of iodine. Cyclocondensation reaction of hydrazides 3 which were obtained in two steps from benzopyrimidinones 2, with some electrophilic species such as 2,4-pentandione, 2,5-hexandione, 1-phenylbutan-1,3-dione and cyclic anyhdrides provided the new compounds 4a-c, 5a-c, 6a-c, 7a-c, 8a-c and 9a-c. The synthesized compounds were characterized by spectroscopic means.

Isocostic Acid, a Promising Bioactive Agent from the Essential Oil of Inula viscosa (L.): Insights from Drug Likeness Properties, Molecular Docking and SAR Analysis.

The chemical composition of the essential oil (LEO) and its volatile fractions (V -V ) collected during the hydrodistillation process every 15 min from the fresh leaves of I. viscosa (L.), growing in Tunisia, were analyzed by GC-FID and GC/MS.

Design and synthesis of novel potent anticoagulant and anti-tyrosinase pyranopyrimidines and pyranotriazolopyrimidines: Insights from molecular docking and SAR analysis.

Pyrimidine-fused compounds are of great interest for the discovery of potent bioactive agents. This study describes the synthesis of novel pyranopyrimidines 3a-f and pyranotriazolopyrimidines 4a-d derivatives via the cyclocondensation reaction of α-functionalized iminoether 2, which was obtained from 2-amino-3-cyanopyrane 1, with a series of primary aromatic amines and hydrazides, respectively. Structures of all synthesized compounds were established on the basis of spectroscopic methods including H NMR, C NMR and ES-HRMS.

Synthesis of imidazo-thiadiazole linked indolinone conjugates and evaluated their microtubule network disrupting and apoptosis inducing ability.

A series of imidazo[2,1-b][1,3,4]thiadiazole linked indolinone conjugates were synthesized and investigated for antiproliferative activity in different human cancer cell lines by changing various substitutions at indolinone and phenyl ring systems. Among them conjugates 7, 14 and 15 were exhibited potent antiproliferative activity with GI values from 0.13 to 3.

Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents.

A new series of 2-aryl 1,2,4-oxadiazolo-benzimidazole conjugates have been synthesized and evaluated for their antiproliferative activity in the sixty cancer cell line panel of the National Cancer Institute (NCI). Compounds 5l (NSC: 761109/1) and 5x (NSC: 761814/1) exhibited remarkable cytotoxic activity against most of the cancer cell lines in the one dose assay and were further screened at five dose concentrations (0.01, 0.

Design and synthesis of imidazo[2,1-b]thiazole-chalcone conjugates: microtubule-destabilizing agents.

A series of chalcone conjugates featuring the imidazo[2,1-b]thiazole scaffold was designed, synthesized, and evaluated for their cytotoxic activity against five human cancer cell lines (MCF-7, A549, HeLa, DU-145 and HT-29). These new hybrid molecules have shown promising cytotoxic activity with IC50 values ranging from 0.64 to 30.

Synthesis and biological evaluation of imidazo[2,1-b][1,3,4]thiadiazole-linked oxindoles as potent tubulin polymerization inhibitors.

A series of imidazo[2,1-b][1,3,4]thiadiazole-linked oxindoles composed of an A, B, C and D ring system were synthesized and investigated for anti-proliferative activity in various human cancer cell lines; test compounds were variously substituted at rings C and D. Among them, compounds 7 ((E)-5-fluoro-3-((6-p-tolyl-2-(3,4,5-trimethoxyphenyl)-imidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene)indolin-2-one), 11 ((E)-3-((6-p-tolyl-2-(3,4,5-trimethoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene)indolin-2-one), and 15 ((E)-6-chloro-3-((6-phenyl-2-(3,4,5-trimethoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl)methylene)indolin-2-one) exhibited potent anti-proliferative activity. Treatment with these three compounds resulted in accumulation of cells in G2 /M phase, inhibition of tubulin assembly, and increased cyclin-B1 protein levels.

Synthesis and cytotoxic activity of 2-anilinopyridine-3-acrylamides as tubulin polymerization inhibitors.

In an attempt to develop potent anticancer agents, a series of 2-anilinonicotinyl-linked acrylamide conjugates were designed, synthesized, and evaluated for cytotoxic activity against various human cancer cell lines, anti-tubulin activity and cell-cycle effects. Among the series, compounds 6 d [(E)-N-(6-fluorobenzo[d]thiazol-2-yl)-3-(2-((3,4,5-trimethoxyphenyl)amino)pyridin-3-yl)acrylamide] and 6 p [(E)-3-(2-((4-methoxyphenyl)amino)pyridin-3-yl)-N-(6-nitrobenzo[d]thiazol-2-yl)acrylamide] showed promising cytotoxicity, specifically against the A549 human lung adenocarcinoma epithelial cell line, with GI50 values of 0.6±0.

Synthesis and biological evaluation of benzo[b]furans as inhibitors of tubulin polymerization and inducers of apoptosis.

A series of benzo[b]furans was synthesized with modification at the 5-position of the benzene ring by introducing C-linked substituents (aryl, alkenyl, alkynyl, etc.). These compounds were evaluated for their antiproliferative activities, inhibition of tubulin polymerization, and cell-cycle effects.