Search

In this study, we report the structural and biological characterization of (2Z,5Z)-5-(4-methyl benzylidene)-3-(2-methylpropyl)-2-(phenylimino)-1,3-thiazolin-4-one (6a) and (2Z,5Z)-5-(3-chlorobenzylidene)-3-(2-methylpropyl)-2-(phenylimino)-1,3-thiazolin-4-one (6b). These compounds were synthesized following the reported method and the molecular structures were confirmed by single-crystal X-ray diffraction studies. Density functional theory (DFT) calculation was carried out to complement the structural and spectral features. In vitro cytotoxicity of the compounds was tested against both the cancerous (SW-480 & MCF-7) and normal (HEK-293) cell lines using the MTT assay. The results indicated that compounds adopted (Z,Z)–configuration with respect to the exocyclic methylene proton and the exocyclic nitrogen. It was observed that compound 6a (IC50 = 190 ± 0.23 μg/mL on SW-480 & IC50 = 330 ± 0.27 μg/mL on MCF-7) showed a weaker anti-proliferative effect than 6b (IC50 = 119.87 ± 0.24 μg/mL on SW-480 & IC50 = 140.39 ± 0.28 μg/mL on MCF-7). These compounds showed acceptable toxicity on normal cell line. [ABSTRACT FROM AUTHOR]

The present work involves a pharmacophore hybridization strategy to combine key biologically active scaffolds. The study led to the synthesis of quinoline based oxadiazole‐triazole conjugates with favorable physicochemical properties as anti‐cancer agents. Among the synthesized compounds 8(a–p), in vitro screening against a panel of four cancer cell lines identified compound 8k, with o‐chloro substitution on the phenyl ring, as potent against human lung carcinoma (A‐549) cells (IC50 =5.6 μM), while showing no significant cytotoxicity upto 200 μM concentration in normal cells. Compound 8 k with o‐chloro substitution induced nuclear morphological changes in A‐549 cells as visualized by DAPI (4,6‐diamidino‐2‐phenylindole) and was shown to bind firmly with A−T rich region in DNA. Changes in DNA topology studied through gel electrophoresis and groove mode of binding to ct‐DNA through multi‐spectroscopic techniques were observed, further validated by molecular docking studies. Overall, the study illustrates successful hybridization strategy leading to compound 8 k as promising anticancer agent for further structural optimization and biological evaluation. [ABSTRACT FROM AUTHOR]

Cassia fistulaLinn. (Fabaceae) fruit has been used in folk medicine and reported for various pharmacological properties. We evaluated the anticancer activity ofC. fistulafruit extracts [ethyl acetate extract of pulp (EEP),n-butanol extract of pulp (BEP), ethyl acetate extract of seeds (EES),n-butanol extract of seeds (BES)] against human cervical cancer (SiHa) and breast cancer (MCF-7) cell lines. Phytochemicals analysis revealed that the EEP and EES contained anticancer compounds like 2(3H)-furanone, rhein, thymoland oleic acid. BES contained inositol and palmitic acid, whereas BEP contained inositol and 2-pyrrolidone. IC50of EEP, EES, BEP and BES against SiHa cells were 415.5±0.19, 435.7±0.11, 535.3±0.32 and 580.2±0.41 µg/mL, whereas against MCF-7 cells were 422.2±0.32, 451.4±0.27, 564.5±0.21 and 575.6±0.47 µg/mL respectively (p ≤ 0.01). At IC50, EEP, EES, BEP and BES treated MCF-7 cells formed colonies of 17.5, 16.3, 22.5 and 18.8 % whereas treated SiHa cells formed colonies of 11.5, 12.8, 19.2 and 16.7 % (p≤0.03). Seeds and pulp treated both cell lines showed up-regulation of p53 and Bax genes, down-regulation of Bcl-2 gene and increased caspase-3, 7 & 10 and -9 enzymes activities. Also, the fragmented genomic DNA in pulp and seeds extracts treated SiHa and MCF-7 cells showed sign of apoptosis.We concluded that the fruit pulp and seeds extracts inhibited MCF-7 and SiHa cells growth and induced cells death by modulating the expression of apoptosis-regulatory genes and caspase enzymes. [ABSTRACT FROM AUTHOR]

Purpose: The tumor suppressor gene PTEN negatively regulates Akt, a downstream mediator phosphoinositol 3-kinase. Several studies have reported the role of PTEN gene in Akt downregulation and apoptosis induction in different cancers and cell lines. However, the role of loss of PTEN expression in Akt activation and spontaneous apoptosis in oral squamous cell carcinoma clinical specimens is not well established. Methods: We investigated the expression of PTEN and phospho-Akt in 146 formalin-fixed (archived) paraffin-embedded oral squamous cell carcinoma tissue sections through immunohistochemical analysis. Programmed cell death (apoptosis) was determined by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling assay. Results: Sixty-one percent loss of PTEN expression and 68.5% Akt activation was observed in oral squamous cell carcinoma. A significant correlation was found between loss of PTEN expression and Akt activation. Loss of PTEN expression and Akt activation were further correlated with different clinical parameters and found to be significantly correlated with tumor stage. Apoptotic index was estimated and correlated with PTEN expression and Akt activation. The percentage of apoptotic cells varied from 0.2 to 14.1%. Low apoptotic index was observed in 105 (72%) of samples, and it was found to be significantly related with loss of PTEN expression and phospho-Akt Conclusion: The present study confirms the contribution of loss of PTEN expression in Akt phosphorylation and spontaneous apoptosis suppression in the specimens of oral cancer. Both PTEN and phospho-Akt are likely to be concerned with oral cancer progression and reduced incidence of spontaneous apoptosis [ABSTRACT FROM AUTHOR]

This study aims to develop chitosan-coated PLGA nanoparticles intended for nose-to-brain delivery of carmustine. Formulations were prepared by the double emulsion solvent evaporation method and optimized by using Box-Behnken Design. The optimized nanoparticles were obtained to satisfactory levels in terms of particle size, PDI, entrapment efficiency, and drug loading. In vitro drug release and ex-vivo permeation showed sustained release and enhanced permeability (approx. 2 fold) of carmustine compared to drug suspension. The AUC 0-t of brain obtained with carmustine-loaded nanoparticles via nasal administration in Albino Wistar rats was 2.8 and 14.7 times that of intranasal carmustine suspension and intravenous carmustine, respectively. The MTT assay on U87 MG cell line showed a significant decrease (P < 0.05) in the IC50 value of the formulation (71.23 μg ml−1) as compared to drug suspension (90.02 μg ml−1).These findings suggest chitosan coated nanoparticles could be used to deliver carmustine via intranasal administration to treat Glioblastoma multiforme. [ABSTRACT FROM AUTHOR]