Some pyrimidohexahydroquinoline candidates: synthesis, DFT, cytotoxic activity evaluation, molecular docking, and in silico studies

• Published in: RSC advances Vol. 14; no. 23; pp. 16584 - 16599
• Main Authors: Ramadan, Sayed K, Abd-Rabboh, Hisham S M, Abdel Hafez, Amal A, Abou-Elmagd, Wael S I
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 15-05-2024; The Royal Society of Chemistry
• Subjects: Binding energy; Bioavailability; Chemical synthesis; Chemistry; Crystallization; Molecular docking; Thiosemicarbazides
• ISSN: 2046-2069; 2046-2069
• DOI: 10.1039/d4ra02271h

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
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
, respectively, which were higher than that of the co-crystallized ligand (LC3) with a binding energy of -8.74 kcal mol
. Besides, the modeling pharmacokinetics disclosed their desirable drug-likeness and oral bioavailability characteristics.