Antiproliferative and genotoxic activities in L929 and HeLa cell lines, mutagenic effects in Salmonella strains of novel benzoxazole derivatives

Some novel fused heterocyclic compounds of 2,5-disubstituted-benzoxazole derivatives, which were previously synthesized by our group, were investigated for their mutagenic properties on Salmonella typhimurium TA 98 and TA 100 strains, cytotoxic activity in L929 and HeLa cell lines by Sulforhodamine B (SRB) cytotoxicity test, and genotoxic potentials in the comet assay. By using Ames/Salmonella assay in the presence of S9 fraction, B22 (5-nitro-2-(p-nitrobenzyl)benzoxazole) was found to be mutagenic in both S. typhimurium TA98 and TA100 strains at all tested doses. IC50 values which were evaluated by SRB cytotoxicity assay revealed that B11 (2-(p-nitrobenzyl)benzoxazole) (IC50 = 99.16 µM) was the most anti-proliferative compound on HeLa cancer cells. Compounds were also tested for their genotoxicity by using comet assay, and it was found that all the compounds had DNA-damaging genotoxic activity on HeLa cells. The comet assay results showed that B11 produced DNA damage at lower concentrations than the other compounds tested on HeLa cancer cells. The results obtained from all the tests suggest that B11 could be a good candidate as a new anticancer agent. © 2016, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved

A study on antiproliferative and genotoxic potentials in L929 and HeLa cell lines - the mutagenic activities in Salmonella strains of novel 2,5-disubstituted-benzoxazole derivatives

41st FEBS Congress on Molecular and Systems Biology for a Better Life -- SEP 03-08, 2016 -- Kusadasi, TURKEYWOS: 000383616900256FEB

Antitumor activities on HL-60 human leukemia cell line, molecular docking, and quantum-chemical calculations of some sulfonamide-benzoxazoles

WOS: 000413975300017PubMed: 27829297We previously synthesized some novel benzoxazole derivatives-containing sulfonamide. In this study, the compounds were investigated for their antitumor activities against the HL-60 human leukemia cells, using the MTT assay. Moreover, quantum chemical calculations using the DFT methods were applied for understanding the difference in antitumor activity. Additionally, molecular docking into active site of the DNA Topo II enzyme was performed on 3QX3. PDB file in order to find out possible mechanism of antitumor effect. According to all obtained results showed that compounds 1b, 1c, and 1d could be potential drug candidates as new antitumor agents, and are promising for cancer therapy.Scientific Research Project of Aksaray University [2014-022]; Scientific Research Project of Ankara University [16H0237002]This study was supported by the Scientific Research Project of Aksaray University [grant number: 2014-022] and the Scientific Research Project of Ankara University [grant number: 16H0237002]

Discovery of 5-(or 6)-benzoxazoles and oxazolo[4,5-b]pyridines as novel candidate antitumor agents targeting hTopo II alpha

Discovery of novel anticancer drugs which have low toxicity and high activity is very significant area in anticancer drug research and development. One of the important targets for cancer treatment research is topoisomerase enzymes. In order to make a contribution to this field, we have designed and synthesized some 5(or 6)-nitro-2-(substitutedphenyl)benzoxazole (1a-1r) and 2-(substitutedphenyl)oxazolo[4,5-b]pyridine (2a-2i) derivatives as novel candidate antitumor agents targeting human DNA topoisomerase enzymes (hTopo I and hTopo II alpha). Biological activity results were found very promising for the future due to two compounds, 5-nitro-2-(4butylphenyl)benzoxazole (1i) and 2-(4-butylphenyl)oxazolo[4,5-b]pyridine (2i), that inhibited hTopo II alpha with 2 mu M IC50 value. These two compounds were also found to be more active than reference drug etoposide. However, 1i and 2i did not show any satisfactory cyctotoxic activity on the HeLa, WiDR, A549, and MCF7 cancer cell lines. Moreover, molecular docking and molecular dynamic simulations studies for the most active compounds were applied in order to understand the mechanism of inhibition activity of hTopo II alpha. In addition, in silico ADME/Tox studies were performed to predict drug-likeness and pharmacokinetic properties of all the tested compounds