Synthesis, Antiproliferative and Cytotoxic Activities, DNA Binding Features and Molecular Docking Study of Novel Enamine Derivatives

Gurdere M. B., AYDIN A., Yencilek B., Erturk F., Ozbek O., ERKAN S., ...Daha Fazla

CHEMISTRY & BIODIVERSITY, cilt.17, sa.7, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 17 Sayı: 7
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1002/cbdv.202000139
  • Dergi Adı: CHEMISTRY & BIODIVERSITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Agricultural & Environmental Science Database, Aquatic Science & Fisheries Abstracts (ASFA), CAB Abstracts, EMBASE, MEDLINE, Veterinary Science Database
  • Anahtar Kelimeler: lactone, chalcone, enamine, antiproliferative activity, cytotoxicity, molecular docking, ANTICANCER ACTIVITY, BIOLOGICAL EVALUATION, CHALCONE DERIVATIVES, CYTO-TOXICITY, GROWTH, CANCER, LUNG, AGENTS, PARTHENOLIDE, LACTONE
  • Yozgat Bozok Üniversitesi Adresli: Evet

Özet

Novel enamine derivatives were synthesized from the reaction of lactone and chalcones and their antiproliferative and cytotoxic activities against six cancer cell lines (e. g., HeLa, HT29, A549, MCF7, PC3 and Hep3B) and one normal cell lines (e. g., FL) were investigated along with their mode of interactions with CT-DNA. Most of the enamine derivatives with IC(50)values of 86-168 mu M demonstrated much stronger antiproliferative activity than the starting molecules against the cancer cells. While, among the enamine derivatives, four compounds displayed higher cytotoxic potency than the control drugs (5-fluorouracil and cisplatin) against the Hep3B cell lines, these compounds did not exhibit any significant toxicity against normal cells, FL. The UV/VIS spectral data suggest that eight compounds cause hypochromism with a slight bathochromic shift (similar to 6 nm), indicating that they bind to the DNA by way of an intercalative or minor groove binding mode. The binding constants of the compounds are in the range of 0.1x103 M-1-2.3x104 M-1. The antiproliferative activity of studied enamine derivatives could possibly be due to their DNA binding as well as their cytotoxic properties. In addition to these assays, the chalcones and enamine derivatives were investigated by molecular docking to calculate the synergistic effect of antiproliferative activities against six human cancer cell lines.