Synthesis, pharmacological evaluation and docking studies of progesterone and testosterone derivatives as anticancer...

Area of Science:

• Medicinal Chemistry
• Cancer Biology
• Pharmacology

Background:

• Steroidal hormones like progesterone and testosterone are implicated in the progression of breast and prostate cancers.
• Developing novel therapeutic agents targeting these cancers is crucial.

Purpose of the Study:

• To synthesize and characterize new nitrogenous derivatives of progesterone and testosterone.
• To evaluate the anti-cancer and anti-inflammatory potential of these novel compounds.

Main Methods:

• Synthesis and characterization of 31 nitrogenous derivatives.
• Anti-cancer activity screening using MTT assay against MCF-7 and PC-3 cell lines.
• Anti-inflammatory activity assessed via oxidative burst inhibition using chemiluminescence.

Main Results:

• Compounds 1-31 demonstrated significant inhibition against both MCF-7 and PC-3 cell lines.
• Compound 17 showed potent activity against MCF-7 (IC50 = 4 ± 0.02 μM), and compound 18 against PC-3 (IC50 = 3.14 ± 0.4 μM).
• Compounds exhibited varying degrees of anti-inflammatory activity, with percent ROS inhibition ranging from 23.2 ± 0.2% to -3.2 ± 4.1%.

Conclusions:

• The novel nitrogenous derivatives of progesterone and testosterone possess significant anti-cancer properties.
• These compounds also display promising anti-inflammatory effects.
• Molecular docking suggests the compounds inhibit cancer cells by binding to enzyme active sites.