Abstract
Camptothecin (CMT) is an anti-tumour alkaloid drug exhibiting selective topoisomerase-I inhibitory activity by eventually hindering dynamic functions of DNA duplex via initiating apoptosis. Unravelling the binding mechanism of CMT with bio macromolecular systems can offer fundamental information regarding the mechanism of actions which can lead to the design of rational proactive drugs. This study endeavoured the binding interactions of CMT with calf thymus DNA (ct-DNA) along with the structural alterations attained by the DNA duplex owing to CMT interactions through multi-spectroscopic, calorimetric and molecular docking studies. The UV–visible absorbance and fluorescence quenching studies revealed the binding strength of CMT with ct-DNA, evident from the binding constants K1 = 3.79 × 103 M−1 and Kq = 2 × 103 M−1. The time-resolved lifetime measurements inferred that the quenching was static due to the non-fluorescent ground state complex formation. The dye displacement study, temperature melting and viscosity measurements established a typical non-intercalative binding mode of CMT with ct-DNA. The binding isotherm deduced from ITC was found to be spontaneous and exothermic exerting a promising ΔG value of −6.2 kcal mol−1. The thermal kinetic parameters implied that the forces primarily involved in the CMT-ct-DNA complexation are hydrogen bonding and van der Waals interactions. Moreover, the structural alterations of DNA duplex reflected in the CD and FTIR spectra could undeniably confirm the groove binding manner of CMT. The in silico extra precision docking study explored more accurate molecular illustrations of sequence specific minor groove binding mechanism evolved between CMT and DNA corroborating well with the experimental results. These innovative findings may shorten the path towards the development of novel and more effective CMT drug derivatives.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.