Some pyrimidohexahydroquinoline candidates: synthesis, DFT, cytotoxic activity evaluation, molecular docking, and in silico studies.
Sayed K RamadanHisham S M Abd-RabbohAmal A Abdel HafezWael S I Abou-ElmagdPublished in: RSC advances (2024)
Some hexahydroquinoline candidates were prepared by reacting 2-amino-3-cyano-1-cyclohexylhexahydroquinoline with oxalyl chloride and triethyl orthoformate. The computational chemical approach agreed with the product-testing results. The produced substances were examined in vitro for their antiproliferative activity against liver carcinoma (HepG2), breast adenocarcinoma (MCF7), prostate cancer (PC3), and colon cancer (HCT116) cell lines. The highest potency against the four cell lines was exhibited by hydrazide, thiosemicarbazide, and thiazolidinone derivatives. The best docking score was presented by thiosemicarbazide and thiazolidinone derivatives as they showed the highest binding to the Mcl-1 enzyme with binding energies of -8.97 and -8.90 kcal mol -1 , respectively, which were higher than that of the co-crystallized ligand (LC3) with a binding energy of -8.74 kcal mol -1 . Besides, the modeling pharmacokinetics disclosed their desirable drug-likeness and oral bioavailability characteristics.
Keyphrases
- molecular docking
- molecular dynamics simulations
- prostate cancer
- density functional theory
- squamous cell carcinoma
- molecular dynamics
- radical prostatectomy
- dna binding
- breast cancer cells
- binding protein
- emergency department
- locally advanced
- small molecule
- protein protein
- cell proliferation
- transcription factor
- adverse drug
- radiation therapy
- rectal cancer