Author/Authors :
Khoshneviszadeh, Mehdi Medicinal and Natural Products Chemistry Research Center - Shiraz University of Medical Sciences - Shiraz, Iran , Firuzi, Omidreza Medicinal and Natural Products Chemistry Research Center - Shiraz University of Medical Sciences - Shiraz, Iran , Aminsafaee, Malihe Medicinal and Natural Products Chemistry Research Center - Shiraz University of Medical Sciences - Shiraz, Iran , Kashefizadeh, Masoud Medicinal and Natural Products Chemistry Research Center - Shiraz University of Medical Sciences - Shiraz, Iran , Ranjbar, Sara Pharmaceutical Sciences Research Center - Shiraz University of Medical Sciences - Shiraz, Iran , Rezaei, Zahra Department of Medicinal Chemistry - Faculty of Pharmacy - Shiraz University of Medical Sciences - Shiraz, Iran , Sadeghpour, Hossein Department of Medicinal Chemistry - Faculty of Pharmacy - Shiraz University of Medical Sciences - Shiraz, Iran , Zargari, Farshid Medicinal and Natural Products Chemistry Research Center - Shiraz University of Medical Sciences - Shiraz, Iran , Miri, Ramin Medicinal and Natural Products Chemistry Research Center - Shiraz University of Medical Sciences - Shiraz, Iran , Edraki, Najmeh Medicinal and Natural Products Chemistry Research Center - Shiraz University of Medical Sciences - Shiraz, Iran
Abstract :
Novel phenanthro-triazine-3-thiol derivatives were designed as potential DNA intercalators
and Bcl-2 inhibitors. After being synthesized, the compounds were evaluated for their cytotoxic
activity against MOLT-4 (human acute lymphoblastic leukemia) and MCF-7 (human breast
adenocarcinoma) cells by MTT assay. P1 (bearing hydrogen substitution) was the most potent
derivative against MOLT-4 with an IC50 value of 7.1 ± 1.1 μM, whereas P11 (bearing phenyl
substitution) demonstrated considerable cytotoxicity against MCF-7 with an IC50 value of 15.4
± 2.9 μM. Compounds P7, P8, P14 and P15 exhibited moderate cytotoxic effects. Furthermore,
to confirm the potential DNA intercalation and Bcl-2 inhibitory activities of phenanthro-triazine
scaffolds, molecular docking analysis was performed. Molecular docking studies indicated that
these compounds not only bind to DNA by intercalation mainly through stacking interactions but
also are well accommodated in the active site of Bcl-2. Therefore, P1 and P11 having phenanthrotriazine-
3-thiol scaffold could be presented as cytotoxic agents with dual DNA intercalation and
Bcl-2 inhibitory activities.
Keywords :
Molecular docking , Antiproliferative effect , Phenanthrene , Triazine , Cancer
