STUDY OF THE INTERACTION OF C-MYC G QUADRUPLEX FORMING DNA SEQUENCE WITH SMALL MOLECULES

Abstract

DNA exhibits a polymorphic nature, manifesting several structures. Guanine-rich DNA sequences present in the promoter region of oncogenes and telomeric regions consist of guanine repeats that enable the formation of guanine quadruplexes stabilized by Hoogsteen hydrogen bonding. The c-MYC G quadruplex DNA, with its multiple guanine repeats, adopts a parallel G quadruplex structure. The focus on the interaction between small molecules and G quadruplexes stems from their significance in molecular recognition and the design of therapeutic drugs. The potential of stabilizing G-quadruplex structures in the promoter regions of oncogenes through small molecule binding has been highlighted as a promising approach for cancer therapy. This study aims to elucidate the interaction between c-MYC G quadruplex DNA and three small molecules, a chemotherapy drug doxorubicin, a chlorin compound 5,10,15,20-Tetraphenyl-[2,3]-[bis(carboxy)-methano]chlorin (H2TPC(DAC)) and resveratrol a natural stilbene flavonoid compound. The study employed three distinct molecules: doxorubicin, an anthracycline, is part of a class of molecules used for cancer therapeutics. Extensive research in the literature supports the potential of aromatic/anthracycline ring-containing compounds as therapeutic agents targeting c-MYC G quadruplex DNA. The second compound, H2DAC, is a reduced porphyrin or chlorin. Its synthesis was guided by the investigation of porphyrin ring-containing compounds and their interactions with G quadruplex-forming DNA sequences. The substantial aromatic ring surface area of H2DAC provides an advantageous site for interaction with G quadruplex DNA. Resveratrol, a natural compound found in the skin of berries and grapes, was explored for its interaction with c-MYC G quadruplex DNA. This natural compound, known for its potential as an anticancer agent, effectively binds with its aromatic ring to G quadruplex DNA. In this investigation, a combination of electronic spectroscopy techniques (ultraviolet-visible, fluorescence, circular dichroism), along with differential scanning calorimetry and molecular modelling, has been employed to examine the interactions.