Two hundred and fifty women, randomly selected from the patients of Maternal and Childhood Centers in Ismailia, were examined gynecologically and interviewed to investigate their psychosexual activity. Results showed that the 80% who were circumcised, complained more significantly of dysmenorrhea (80.5%), vaginal dryness during intercourse (48.5%), lack of sexual desire (45%), less frequency of sexual desire per week (28%), less initiative during sex (11%), being less pleased by sex (49%), being less orgasmic (39%), and less frequency of orgasm (25%), and having difficulty reaching orgasm (60.5%) than the uncircumcised women. However, other psychosexual problems, such as loss of interest in foreplay and dyspareunia, did not reach statistical significance. The study suggests that circumcision has a negative impact on a woman's psychosexual life.

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The tumor resistance to p53 activators posed a clinical challenge. Combination studies disclosed that concomitant administration of Bcl2 inhibitors can sensitize the tumor cells and induce apoptosis. In this study, we utilized a rapid synthetic route to synthesize two novel hybrid spirooxindole-based p53-MDM2 inhibitors endowed with Bcl2 signaling attenuation. The adducts mimic the thematic features of the chemically stable potent spiro [3H-indole-3,2′-pyrrolidin]-2(1H)-ones p53-MDM2 inhibitors, while installing a pyrrole ring via a carbonyl spacer inspired by the natural marine or synthetic products that efficiently inhibit Bcl2 family functions. A chemical insight into the two synthesized spirooxindoles including single crystal x-ray diffraction analysis unambiguously confirmed their structures. The synthesized spirooxindoles 2a and 2b were preliminarily tested for cytotoxic activities against normal cells, MDA-MB 231, HepG-2, and Caco-2 via MTT assay. 2b was superior to 5-fluorouracil. Mechanistically, 2b induced apoptosis-dependent anticancer effect (43%) higher than that of 5-fluorouracil (34.95%) in three studied cancer cell lines, activated p53 (47%), downregulated the Bcl2 gene (1.25-fold), and upregulated p21 (2-fold) in the treated cancer cells. Docking simulations declared the possible binding modes of the synthesized compounds within MDM2.

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