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Breast cancer is a common type of cancer among females, as it represents 32% of the diagnosed cases in the United States. In the hormone-sensitive kind of breast cancer, the endogenous estrogen is a known promoter for the growth and metastasis of cancerous cells. As age is a major risk factor for the development of breast cancer, this type of cancer is most frequent among postmenopausal women, where estrogen is primarily produced outside the ovaries with the aid of the aromatase enzyme. Therefore, several aromatase inhibitors (AIs) like letrozole and anastrozole were employed for the treatment of estrogen-dependent breast cancer in postmenopausal females. However, the incidence of drug resistance and several side effects are complicating AIs therapy. As such, the objective of this study is to computationally screen a group of phytocompounds against aromatase cytochrome P450 enzyme. Both molecular docking and dynamics simulation tools were used for the structure-based virtual screening to identify new AIs candidates. For this screening, the best results did include three flavonoids (Amentoflavone, Bilobetin, Ginkgetin) and two alkaloids (Irinotecan, Liensinine). Depending on these results, the already approved anticancer chemotherapy Irinotecan is anticipated to have a high drug-likeness score and acceptable pharmacokinetics. Also, docking study pointed to the mostly hydrophobic nature of interactions between Irinotecan and aromatase enzyme. Moreover, the computed binding energy of molecular mechanic-Poisson Boltzmann surface area (MM-PBSA) for Irinotecan during simulation was -10.78 Kcal/ mol and it was one of the best reported values. Finally, the in-vitro anticancer activity of Irinotecan was with micromolar range against susceptible breast cancer cell line.
Hasanain Abdulhameed Odhar (Tue,) studied this question.