Target ß-catenin/CD44/Nanog axis in colon cancer cells by certain N'-(2-oxoindolin-3-ylidene)-2-(benzyloxy)benzohydrazides.

Cell surface molecule CD44 plays a major role in regulation of cancer stem cells CSCs on both phenotypic and functional level, however chemical inhibition approach of CD44 to targets CSCs is poorly studied. Herein, we report the discovery of certain N'-(2-oxoindolin-3-ylidene)-2-(benzyloxy)benzohydrazides as a novel inhibitor of CD44. Molecular docking study showed interference of the scaffold of these compounds with ß-catenin/TCF-4 complex, building a direct relationship between CD44 inhibition and observed well-fitted binding domain. Compound 11a, most potent member elicits inhibition effect on TCF/LEF reporter activity conformed the involvement of Wnt pathway inhibition as a mechanism of action. Furthermore, the treatment by the mentioned compound leads to inhibition of embryonic transcriptional factor Nanog but not Sox2 or Oct-4 suggested specific targeted effect. Moreover, the cytotoxicity and cell cycle effect of this series seems to be dependent on CD44 expression.

Novel ethyl 1,5-disubstituted-1H-pyrazole-3-carboxylates as a new class of antimicrobial agents.

A series of pyrazole derivatives 9-22 were designed and synthesized. All the newly synthesized compounds were assayed for their antimicrobial activity against the Grampositive bacteria Staphyllococcus aureus and Bacillius subtilis and the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, in addition to the fungi organisms, Candida albicans, C. parapsilosis and C. tropicalis. Ethyl 5-(2,5-dimethylthiophen-3-yl)-1-phenyl-1H-pyrazole-3-carboxylate (21) (MIC(E.coli) = 0.038 µmol mL⁻¹, MIC(P. aerug.) = 0.067 µmol mL⁻¹) is nearly as active as ampicillin (MIC = 0.033 and 0.067 µmol mL⁻¹), respectively. Ethyl 5-(4-bromo-2-chlorophenyl)-1-phenyl-1H-pyrazole-3-carboxylate (16) (MIC = 0.015 µmol mL⁻¹) is more active than fluconazole (0.020 µmol mL⁻¹) as a reference drug against C. parapsilosis.

Design and synthesis of new cholesterol-conjugated 5-Fluorouracil: a novel potential delivery system for cancer treatment.

Cholesterol-conjugated 5-fluorouracil prodrugs were designed to be carried in vivo via low density lipoproteins (LDL) and subsequently undergo LDL-receptor-mediated internalisation into cancer cells. In vivo anti-cancer evaluation was performed using 5-fluorouracil-cholesterol conjugate in a mouse model. The obtained prodrugs were more potent than 5-fluorouracil control drug at the same 5-fluorouracil content (3 mg·kg-1).

Targeting cancer using cholesterol conjugates.

Conjugation of cholesterol moiety to active compounds for either cancer treatment or diagnosis is an attractive approach. Cholesterol derivatives are widely studied as cancer diagnostic agents and as anticancer derivatives either in vitro or in vivo using animal models. In largely growing studies, anticancer agents have been chemically conjugated to cholesterol molecules, to enhance their pharmacokinetic behavior, cellular uptake, target specificity, and safety. To efficiently deliver anticancer agents to the target cells and tissues, many different cholesterol-anticancer conjugates were synthesized and characterized, and their anticancer efficiencies were tested in vitro and in vivo.