A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II.

Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber's rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.

The possible protective effect of Bougainvillea spectabilis leaves extract on estradiol valerate-induced polycystic ovary syndrome in rats (biochemical and histological study)

Polycystic ovary syndrome (PCOS) is a reproductive and metabolic disorder in which the level of oxidative elements in blood rises. Bougainvillea spectabilis is a plant with a potent antioxidant effect, since it contains flavonoids. The aim of this work is to explore the possible protective potency of Bougainvillea spectabilis leaves (BSL) extract on ovarian folliculogenesis using a rat model of estradiol valerate (EV) - induced PCOS. Thirty six mature female rats were divided into four groups: 1. Control group (six rats). 2. EV group (ten rats), singly injected with 2mg/kg EV subcutaneously. 3. BSL group (ten rats), given 100mg/kg BSL extract orally for 30 days. 4. EV + BSL group (ten rats), singly injected with EV subcutaneously and given 100mg/kg BSL extract orally for 30 days. Biochemical measurements of serum levels of estrogen, testosterone, LH, FSH, glucose, totals lipids, and total antioxidants were done using ELISA method. Histological (using hematoxylin & eosin and Masson's trichrome stains) and immunohistochemical (using anti cyclooxygenase 2 {COX 2}) studies were performed. This was followed by morphometric measurements and statistical analysis. PCOS caused massive primordial follicle loss and development of cystic follicles with increase in fibrosis, COX 2 immunoexpression. There was a significant reduction in LH, estrogen and glucose serum levels and increase in FSH and the antioxidant serum levels between the EV + BSL-extract-treated group compared to EV-treated group. Histomorphometric studies also showed the significant changes in the number of follicles and decreased cyst formation in the combined therapy group. There was a significant role of BSL extract in restoration of ovarian folliculogenesis and reduction of biochemical, histological and immunohistochemical changes in EV treated group

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