STUDIES ON THE INTERACTION OF FLAVONES WITH DIFFERENT DNA SEQUENCES AND THEIR STRUCTURAL ANALYSIS

Abstract

Deoxyribonucleic acid (DNA) is a molecule of enormous biological significance. It is involved in numerous biological processes, like transcription and replication, that play a vital role in the growth and development of organisms. Regions of DNA engaged in many critical functions, such as the origin of replication and transcription of the promoters, are of specific interest as targets of many anticancer and antibiotic drugs. Several therapeutic agents are capable of sequence-specific interaction with double-stranded DNA. Small molecule-DNA interaction is an exciting research area for developing various therapeutic molecules and has received much attention in medicinal chemistry and pharmaceuticals. Molecules that bind to DNA noncovalently generally interact through intercalation or groove binding mode. Intercalative binders cause major structural changes in DNA, restricting the DNA from binding to its targets. Groove binder molecules generally cause slight perturbations in DNA structure and can inhibit the binding to many transcription factors, thereby blocking many molecular processes. Flavones are naturally occurring molecules that belong to the flavonoid group, widely present in fruits and vegetables. Flavones are distinguished by the number and position of the hydroxyl group on the aromatic ring A of the basic structure. Flavone is the simplest compound in this class. Baicalein and chrysin are two other molecules in this group. They possess many biological functions, including antioxidant, anti-inflammatory, antimicrobial, antiviral, and anticancer activities. These properties can provide insight into their association with biomolecules like proteins, enzymes, and DNA. The present thesis gives comprehensive details of sequence-specific interactions between flavone molecules and different forms of DNA, such as CT DNA, d(CCAATTGG)2, and d(CACGTG)2 DNA sequences. CT DNA is used as model DNA with base pairs heterogeneity and no sequence specificity for binding interactions. The sequences are widely present in the promoter regions of many organisms. They are present in many physiologically essential genes, such as tumour suppressor gene p53, oncogenes, and transcription factors. The binding of small molecules in a sequence-specific manner is critical in controlling the several transcription factors responsible for tumour generation. Flavones are naturally occurring molecules of our daily diet, effectively binding to these sequences, which can inhibit DNA replication and DNA-protein interactions. The binding mechanism between flavone molecules and DNA sequence has not been well understood, and three-dimensional X-ray and solution NMR structures of flavones-DNA sequences have not been reported.