Preparation of Dearomatized p-Coumaric Acid Derivatives as DNA Damage Response Inhibitors with Potent In Vitro Antitumor Effect.

Our research group previously identified graviquinone (1) as a promising antitumor metabolite that is formed in situ when the antioxidant methyl caffeate scavenges free radicals. Furthermore, it exerted a DNA damaging effect on cancer cells and a DNA protective effect on normal keratinocytes. To expand and explore chemical space around qraviquinone, in the current work we synthesized 9 new alkyl-substituted derivatives and tested their in vitro antitumor potential.

Stereoselective synthesis of new type of estradiol hybrid molecules and their antiproliferative activities.

To prepare new type of estrane hybrid molecules, we chose 3-methoxy- and 3-benzyloxy-17β,16β-epoxymethylene-estra-1,3,5(10)-trienes as starting materials (2 and 5). These steroid oxetanes were transformed with ethylene glycol in the presence of BF.OEt into 3-methoxy- and 3-benzyloxy-16β-(2'-oxa-4'-hydroxy)butyl-17β-hydroxy-estra-1,3,5(10)-trien-17β-ols (3a and 6a).

Antiproliferative Properties of Newly Synthesized 19-Nortestosterone Analogs Without Substantial Androgenic Activity.

19-Nortestosterone C-17 epimers with prominent antiproliferative properties have been previously described. In our present study, five novel 17α-19-nortestosterones () were synthesized to increase their beneficial biological activities with no associated undesired hormonal effects. The compounds were screened by a viability assay against a panel of human adherent gynecological cancer cell lines.

Antiproliferative and Antimicrobial Activities of Selected Bryophytes.

One-hundred and sixty-eight aqueous and organic extracts of 42 selected bryophyte species were screened in vitro for antiproliferative activity on a panel of human gynecological cancer cell lines containing HeLa (cervix epithelial adenocarcinoma), A2780 (ovarian carcinoma), and T47D (invasive ductal breast carcinoma) cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and for antibacterial activity on 11 strains using the disc-diffusion method. A total of 99 extracts derived from 41 species exerted ≥25% inhibition of proliferation of at least one of the cancer cell lines at 10 μg/mL. In the cases of , , , , , and , more than one extract was active in the antiproliferative assay, whereas the highest activity was observed in the case of .

Microwave-assisted stereoselective approach to novel steroidal ring D-fused 2-pyrazolines and an evaluation of their cell-growth inhibitory effects in vitro.

Novel ring D-condensed 2-pyrazolines in the Δ(5)-androstene series were efficiently synthesized from 16-dehydropregnenolone or its acetate with different arylhydrazines or methylhydrazine, respectively, under microwave irradiation. The reactions are assumed to occur via hydrazone intermediates, followed by intramolecular 1,4-addition leading to the fused heteroring stereoselectively with a 16α,17α-cis ring junction. The synthesized compounds were subjected to in vitro pharmacological studies of their antiproliferative activities against four human breast (MCF7, T47D, MDA-MB-231 and MDA-MB-361) and three cervical (HeLa, C33A and SiHA) malignant cell lines.

Stereocontrolled synthesis of the four 16-hydroxymethyl-19-nortestosterone isomers and their antiproliferative activities.

Novel 16-hydroxymethyl-19-nortestosterone diastereomers were prepared by Birch reduction from the corresponding 3-methoxy-16-hydroxymethylestra-1,3,5(10)-trien-17-ol isomers with known configurations. The synthesized compounds are 16α- and 16β-hydroxymethyl-substituted 19-nortestosterone and their 17α-epimers. To prepare 17α-19-nortestosterone, the Mitsunobu inversion reaction of 19-nortestosterone with different alkyl and aryl carboxylic acids was chosen.