Bioorganic and Medicinal Chemistry Letters p. 3440 - 3446 (2014)
Update date:2022-07-29
Topics:
Rizvi, Masood Ahmad
Guru, Santosh
Naqvi, Tahira
Kumar, Manjeet
Kumbhar, Navanath
Akhoon, Showkat
Banday, Shazia
Singh, Shashank K.
Bhushan, Shashi
Mustafa Peerzada
Shah, Bhahwal Ali
A target synthesis of a library of symmetric aromatic diselenides was attempted with the aim of generating anticancer lead compounds. Out of thirteen screened molecules (1-13) against a panel of human cancer cell lines, compound 8 exhibited highest cell growth inhibition in Human leukemia HL-60 cells with IC50 value of 8 μM. Compound 8 had a good pro-apoptotic potential as evidenced from several apoptotic protocols like DNA cell cycle analysis and monitoring of apoptotic bodies formation using phase contrast and nuclear microscopy with Hoechst 33,258. Also, 8 significantly inhibits S phase of the cell cycle and eventually trigger apoptosis in HL-60 cells through mitochondrial dependent pathway substantiated by the loss of mitochondrial potential. A theoretical investigation of DNA binding ability of 8 showed that it selectively bind to minor groove of DNA, where it is stabilized by hydrogen bonding and hydrophobic interactions.
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Doi:10.1039/c4dt00820k
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