Crtice

https://doi.org/10.5562/cca2662

Synthesis, Crystal Structure and in vitro DNA Binding Studies of Combretastatin A-4 Analogue

Masood Ahmad Rizvi orcid.org/0000-0003-0470-6329 ; Department of Chemistry, University of Kashmir, Hazratbal Srinagar,190006, J&K, India
Yuvraj Dangat ; Physical Chemistry Division, CSIR-National Chemical Laboratory, Pune - 411008, India
Zahid Yaseen ; Department of Civil Engineering, Islamic University of Science and Technology, Kashmir 192122, India
Vivek Gupta ; Department of Physics, University of Jammu, Babasaheb Ambedkar Road, New Campus, Jammu Tawi - 180 006, J&K, India
Khaliquz Zaman Khan ; Department of Chemistry, University of Kashmir, Hazratbal Srinagar,190006, J&K, India

Sažetak

Synthesis of a novel Combretastatin A-4 analogue using Schiff’s reaction of benzil and 4-aminoantipyrine has been achieved under solvent free conditions. The structure of compound was examined spectroscopically and confirmed from single crystal diffraction studies. The synthesized Combretastatin A-4 analogue was investigated for its DNA binding ability as the plausible mechanism for its antitumor activity. The binding propensity of the synthesized compound with calf-thymus (CT) DNA was monitored with absorption and emission spectrophotometric titrations. The calculations predict a binding constant of 7.24×104 for the complex of the synthesized compound with CT DNA which is comparable in magnitude to that of DNA binding of bactericidal drug enoxacin and typical intercalation indicator ethidium bromide (EB). Competitive binding studies of the synthesized compound with EB using fluorescence titration reveal that it displaces the DNA-bound EB and binds in intercalative mode which was further supported by circular dichroism (CD) spectroscopy. The probable site and binding energy of the compound with DNA was further theoretically investigated by molecular docking studies. The significant DNA binding ability of the synthesized Combretastatin A4 analogue as revealed from this study could be related to the anticancer activity of the Combretastatin A4.

Ključne riječi

crystal structure; DNA binding; combretastatin A-4; benzil; bio-physical; phenazones; fluorescence; ethidium bromide

Hrčak ID:

150534

URI

https://hrcak.srce.hr/150534

Datum izdavanja:

30.12.2015.

Posjeta: 2.262 *