Synthetic Naphthoquinone Derivatives as Anticancer Agents in Ovarian Cancer: Cytotoxicity Assay and Investigation of Possible Biological Mechanisms Action.

In this study, eight naphthoquinone derivatives were synthesized in yields ranging from 52 to 96% using easy, fast, and low-cost methodologies. All naphthoquinone derivatives were screened for their in vitro anti-proliferative activities against OVCA A2780 cancer cell lines. Amongst all analysed compounds, derivatives 3-5 presented the most prominent cytotoxic potential. Naphthoquinones 3 and 4, bearing sulfur-containing groups, were identified as having high potential for ROS production, in particular the superoxide anion. Furthermore, 3 and 4 compounds caused a decrease in the cell population in G0/G1 and induced more than 90% of the cell population to apoptosis. Compound 5 did not act in any of these processes. Finally, compounds 3-5 were tested for their inhibitory ability against PI3K and MAPK. Compounds 3 and 4 do not inhibit the PI3K enzyme. On the other hand, the naphthoquinone-polyphenol 5 was only able to inhibit the percentage of cells expressing pERK.

Synthetic enamine naphthoquinone derived from lawsone as cytotoxic agents assessed by in vitro and in silico evaluations.

We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 < 24 µM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C2-C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as anticancer molecules by inhibiting topoisomerase-II and thymidylate synthase.

Synthesis, docking, machine learning and antiproliferative activity of the 6-ferrocene/heterocycle-2-aminopyrimidine and 5-ferrocene-1H-Pyrazole derivatives obtained by microwave-assisted Atwal reaction as potential anticancer agents.

A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the optimization of the reaction conditions, eight 2-aminolpyrimidines containing ferrocene and heterocycles and three ferrocene pyrazoles were synthesized from the respective chalcones in good yields. Eight compounds had their structure determined by X-ray diffraction. The molecular hybrid 6a-h and 9a-c were tested on four cancer cell lines - HCT116, PC3, HL60 and SNB19 - where four pyrimidine 6a, 6f-h and one pyrazole 9c derivatives show promising antiproliferative activity. In addition, docking simulation and machine learning methods were carried out to explain the biological activity achieved by the synthetized compounds.

2H-1,2,3-Triazole-chalcones as novel cytotoxic agents against prostate cancer.

Prostate cancer is an important cause of death in the male population and for which there is no satisfactory chemotherapy. Herein a new series of chalcone hybrids containing 2H-1,2,3-triazole core as the ring B has been synthesized and evaluated in vitro against PC-3 prostate cancer cell line. Compounds 4a, 4c and 4e significantly reduced cell viability and showed IC50 of 28.55, 15.64 and 25.56 µM, respectively. The structure-activity relationship supported by computational chemistry points that the polarity of the molecular surface area should have some relevance to the efficiency of the compounds, in particular the ratio of the partial positive charge sites and the total molecular surface area exposed to the cell environment.