Novel Dorsomorphin Derivatives: Molecular Modeling, Synthesis, and Bioactivity Evaluation.

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Pharmacology

Background:

• Dorsomorphin inhibits the bone morphogenetic protein (BMP) pathway.
• Further investigation of dorsomorphin derivatives' antiproliferative activity is needed.

Purpose of the Study:

• Synthesize novel dorsomorphin derivatives.
• Evaluate their antiproliferative effects on cancer and endothelial cells.
• Identify potent bioactive leads.

Main Methods:

• Chemical synthesis of dorsomorphin derivatives.
• Molecular docking studies.
• In vitro antiproliferative assays on L1210, CEM, HeLa, HMEC-1, and BAEC cell lines.

Main Results:

• Diphenol 22 exhibited IC50 values below 9 μM in most tested cell lines.
• Carbamate derivative 6 potently inhibited bovine aortic endothelial cell proliferation.
• Identified novel compounds with significant antiproliferative potential.

Conclusions:

• The study presents promising antiproliferative dorsomorphin derivatives.
• Diphenol 22 and carbamate 6 are identified as potential lead compounds.
• Results provide a basis for further development of dorsomorphin-based therapeutics.