Novel (±)---lactam ureas: Synthesis, and biological profiling.

A diastereomeric mixture of racemic 3-phthalimido--lactam / was synthesized by the Staudinger reaction of carboxylic acid activated with 2-chloro-1-methylpyridinium iodide and imine . The amino group at the C3 position of the -lactam ring was used for further structural upgrade. --lactam ureas were prepared by the condensation reaction of the amino group of -lactam ring with various aromatic and aliphatic isocyanates. Antimicrobial activity of compounds was evaluated and neither antibacterial nor antifungal activity were observed. Several of the newly synthesized --lactam ureas , , , , , , and were evaluated for antiproliferative activity against liver hepatocellular carcinoma (HepG2), ovarian carcinoma (A2780), breast adenocarcinoma (MCF7) and untransformed human fibroblasts (HFF1). The -lactam urea showed the most potent antiproliferative activity against the ovarian carcinoma (A2780) cell line. Compounds and exhibited strong cytotoxic effects against human non-tumor cell line HFF1. The -lactam ureas were estimated to be soluble and membrane permeable, moderately lipophilic molecules (log 4.6) with a predisposition to be CYP3A4 and P-glycoprotein substrates. The tools PASS and SwissTargetPrediction could not predict biological targets for compounds with high probability, pointing to the novelty of their structure. Considering low toxicity risk, molecules and can be selected as the most promising candidates for further structure modifications.