Search

Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC50 of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy. [ABSTRACT FROM AUTHOR]

In order to obtain potential anticancer agents, hybrid compounds have been synthesized by coupling thiazolidinone and pyrazole scaffolds. Among the synthesized compounds, 2-(1,3-diphenyl-1H-pyrazol-4-yl)-3-phenyl thiazolidin-4-one (4a) was found to be the most potent based on a docking (−9.307) and binding scores (−66.46), along with good ADME parameters. In vitro anticancer activity of compound 4a shows a maximum inhibition against lung cancer (NCI-H23) cell lines with a moderate inhibition rate of 31.01%. Molecular docking studies revealed that these hybrid compounds bind well to the active site of peroxisome proliferator-activated receptors-gamma (PPAR-gamma). Doxorubicin was used as a positive control. It can be concluded that 4a having pyrazole-thiazolidinone ring systems has the potential to be developed as an anticancer agent. [ABSTRACT FROM AUTHOR]

In the present study, a novel series of new furanone-based benzothiazole derivatives (4a-j) were synthesized from 4-(benzo[d]thiazol-2-yl)-4-oxobutanoic acid (3) as potential anticancer agents. In vitro cytotoxicity against three human cancer cell lines (A549, MCF7, and DUI45) revealed substantial activity. Di-substituted compound, 4i emerged as a promising anticancer compound which showed IC50 values of 7.2 ± 0.5, 6.6 ± 1.4, and 7.3 ± 0.1 µM against A549, MCF7, and DUI45 cell lines, respectively. Four compounds 4c, 4e, 4f, and 4i evaluated for their acute toxicity were found to be non-toxic on the two vital organs (liver and heart). Further, these compounds were found to be more efficient and less hepatotoxic in comparison to standard drug doxorubicin. Molecular docking studies carried out with VEGFR-2 revealed compounds 4a and 4i as potential VEGFR-2 kinase inhibitors. In silico ADME evaluation was carried out to estimate and predict drug-likeness. Compound 4i demonstrated the best ADME parameters. Based on the results of docking analyses, ADME, and in vitro cytotoxicity, compound 4i is identified as the lead compound for further development of anticancer agents. [ABSTRACT FROM AUTHOR]