الفهرس 
1. IntroductionOnly 14 pages are availabe for public view
 |  | from | 170 |  |  |
| | | from | 170 | | |
Abstract
Modification of steroid molecules by introducing heterocyclic ring into the core structure of
steroids has been utilized as an attractive approach for either cancer prognosis or diagnosis.
Several newly cholestanoheterocyclic steroids were synthesized, analytical and spectral data
proved the validity of the novel synthesized steroid derivatives. The cytotoxicity of the
synthesized compounds 3, 4, 5, 7, 9, 10, 13, 15b, and 16b were evaluated using human
colorectal cancer HCT 116 and Caco-2, cervical cancer HeLa, hepatoma HepG2, and breast
cancer MCF7 cell lines. Intriguingly, compound 13 has the highest cytotoxic effect when
applied on the majority of cancer cells. In conclusion compound 13 may be considered as a
promising anti-cancer candidate against all cancer cell lines, because it recorded the lowest
IC50 of the majority of the used cancer cell lines. Furthermore, molecular-docking study was
employed to determine the binding modes against aromatasecytochrome P450 (CYP19),
cyclin dependent kianse 2 (CDK2), and B-cell lymphoma (BCL-2) proteins, which are major
proteins involved in pathogenesis of cancer. Molecular-docking analyses revealed that
compounds 13, 3 and 5 (free energy of binding = -9.2, -9.1, and -9.0 Kcal/mole, respectively)
were the best docked ligand against aromatase CYP19, while compounds 16b, 3, 9, and 10
(free energy of binding = -9.6, -9.3, and -9.2 Kcal/mole, respectively) were the best docked
ligand against CDK2, while compounds 15b, 16b, and 13 (free energy of binding = -9.1, -9.0,
and -8.7 Kcal/mole, respectively) were the best docked ligand against BCL2. In conclusion
compounds 3. 13, and 16b were the most promising compounds with lowest IC50s against
most of the tested cancer cell lines, and as it displayed the lowest binding energies, critical
hydrogen bonds and hydrophobic interactions with the three molecular targets compared to
other tested compounds.