New Benzimidazole-Triazole Derivatives as Topoisomerase I Inhibitors: Design, Synthesis, Anticancer Screening, and Molecular Modeling Studies.

In this study, we designed, synthesized, and evaluated a series of 1,2,4-triazole benzimidazoles for their cytotoxic effects against the A549, C6, and NIH3T3 cell lines. Additionally, these compounds were assessed for their inhibitory activity against DNA topoisomerase I, aiming to develop novel anticancer agents. The synthesized final compounds 4a-h were characterized using 1H NMR, 13C NMR, and HRMS. Among them, compounds 4b and 4h emerged as the most potent agents against the A549 cell line, exhibiting an IC50 value of 7.34 ± 0.21 µM and 4.56 ± 0.18 µM, respectively. These results were compared to standard drugs, doxorubicin (IC50 = 12.420 ± 0.5 µM) and Hoechst 33342 (IC50 = 0.422 ± 0.02 µM). Notably, all tested compounds displayed higher cytotoxicity toward A549 cells than C6 cells. Compounds 4b and 4h demonstrated significant inhibitory activity against topoisomerase I, highlighting their potential as lead compounds in anticancer therapy. Subsequent in silico molecular docking studies were conducted to elucidate the potential binding interactions of compounds 4b and 4h with the target enzyme topoisomerase I. Molecular dynamics studies also assessed and validated the binding affinity and stability. These studies confirmed the promising binding affinity of these compounds, reinforcing their status as lead candidates. According to DFT, compound 4b having the lower energy gap value (ΔE = 3.598 eV) is more chemically reactive than the others, which is consistent with significant inhibitory activity against topoisomerase I. Furthermore, in silico ADME profiles for compounds 4b and 4h were evaluated using SwissADME, providing insights into their pharmacokinetic properties.

Design, synthesis and apoptotic effects of novel benzoxazole compounds.

A series of new benzoxazole-hydrazone and benzoxazole-1,3,4-oxadiazole derivatives have been designed, synthesized and evaluated as cytotoxic agents toward human A549 lung cancer cells. Compounds 3d, 3e, 5b, 5c, 5d and 5e were the most potent compounds with IC50 values of <3.9, 10.33, 11.6, 5.00, <3.9 and 4.5 µg/mL, respectively, which are higher than reference drug cisplatin (IC50 = 19.00 µg/mL). The flow cytometry-based apoptosis detection assay was performed to determine their effects on apoptosis in A549 cells. All tested compounds induced apoptosis in A549 cell line.

Design and Synthesis of New 1,3,4-Oxadiazole - Benzothiazole and Hydrazone Derivatives as Promising Chemotherapeutic Agents.

Looking for new cytotoxic and antimicrobial agents with improved antitumor activity, a series of hydrazide and oxadiazole derivatives were designed and synthesized using 3-methoxyphenol as starting substance. Novel N'-(arylidene)-2-(3-methoxyphenoxy)acetohydrazide derivatives (4a-f)/1-(4-substitutedphenyl)-2-[(5-[(3-methoxyphenoxy)methyl]-1,3,4-oxadiazol-2-yl)thio]ethan-1-one derivatives (6a-f)/N-(6-substitutedbenzothiazol-2-yl)-2-[(5-[(3-methoxyphenoxy)methyl]-1,3,4-oxadiazol-2-yl)thio]acetamide derivatives (7a-e) were obtained and evaluated for their in vitro antimicrobial activity against various gram-positive, gram-negative bacteria and fungi. The antimicrobial activity potential of the compounds against gram-negative bacteria was found to have higher compared to the potential against gram-positive bacteria. Also, compounds were screened for their antiproliferative activity against 2 selected human tumor cell lines, A549 lung, MCF7 breast cancer cell line and mouse embryo fibroblast cell line, NIH/3T3 as healthy cell line. Among the compounds evaluated, compound 7c bearing 1,3,4-oxadiazole ring and 6-methoxy benzothiazole moiety exhibited the highest inhibitory activity against A549 and MCF-7 tumor cell lines in contrary to NIH/3T3 cell line, as desired.

Effects of three different irrigating solutions and KTP laser irradiation on apical leakage: an electrochemical study.

OBJECTIVE: The purpose of this study was to evaluate the effect of three different irrigating solutions (17% EDTA, 10% citric acid and 2.5% NaOCl) and KTP laser irradiation on apical leakage using an electrochemical method. MATERIALS AND METHODS: Sixty extracted single-rooted human teeth with mature apices were instrumented up to a size 35 K-file. After using each file and before proceeding to the next, canals were irrigated with 2 ml of 2.5% NaOCl. All teeth were then randomly divided into four groups. In group 1, the root canals were irrigated with a final flush of 17% EDTA. In group 2, the root canals were irrigated with a final flush of 10% citric acid. In group 3, the root canals were irradiated with KTP laser at 1 W, 4.45 J/cm(2). In group 4, the root canals were irrigated with a final flush of 2.5% NaOCl. The root canals were then filled using the cold lateral condensation method. Apical leakage was evaluated using an electrochemical method over a period of 10 days. Data were analysed using Tukey HSD and Friedmann tests with p = 0.05 as the level for statistical significance. RESULTS: The 17% EDTA and 10% citric acid groups had statistically less apical leakage than the 2.5% NaOCl group at days 7, 8, 9 and 10 (p < 0.05); however, no significant differences were found between the tested groups at the other time intervals (p > 0.05). No significant difference was found between the KTP laser group and other groups tested at all time intervals (p > 0.05). CONCLUSION: All groups were unable to eliminate apical leakage. However, final irrigation with 17% EDTA and 10% citric acid following root canal preparation reduced postobturation apical leakage compared with 2.5% NaOCl irrigation. When KTP laser and the other three irrigants were compared, no significant difference was found.