Interaction of the putative anticancer alkaloid chelerythrine with nucleic acids: biophysical perspectives
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REVIEW
Interaction of the putative anticancer alkaloid chelerythrine with nucleic acids: biophysical perspectives Anirban Basu 1
&
Gopinatha Suresh Kumar 2
Received: 29 July 2020 / Accepted: 26 October 2020 # International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Alkaloids represent an important group of molecules that have immense pharmacological potential. Benzophenanthridine alkaloids are one such class of alkaloids known for their myriad pharmacological activities that include potential anticancer activities. Chelerythrine is a premier member of the benzophenanthridine family of the isoquinoline group. This alkaloid is endowed with excellent medicinal properties and exhibits antibacterial, antimicrobial and anti-inflammatory properties. The molecular basis of its therapeutic activity is considered due to its nucleic acid binding capabilities. This review focuses on consolidating the current status on the nucleic acid binding properties of chelerythrine that is essential for the rational design and development of this alkaloid as a potential drug. This work reviews the interaction of chelerythrine with different natural and synthetic nucleic acids like double- and single-stranded DNAs, heat-denatured DNA, quadruplex DNA, double- and single-stranded RNA, tRNA and triplex and quadruplex RNA. The review emphasizes on the mode, specificity, conformational aspects and energetics of the binding that is particularly helpful for developing nucleic acid targeted therapeutics. The fundamental results discussed in this review will greatly benefit drug development for many diseases and serve as a database for the design of futuristic benzophenanthridine-based therapeutics. Keywords Benzophenanthridine alkaloid . Chelerythrine . Nucleic acids . DNA . RNA
Introduction The remarkable progress in the field of molecular biology and biotechnology has led to a paradigm shift towards the development of nucleic acid–based drugs for the treatment of genetic disorders (Saenger 1984; Wilson and Li 2000; Gallego and Varani 2001; Tor 2003; Vicens and Westhof 2003; Giri and Suresh Kumar 2010a, b; Bhadra and Suresh Kumar 2011). Targeting nucleic acids by small molecules has been a key strategy for many recent therapeutic interventions. Understanding the basics of such small molecule–nucleic acid interactions will facilitate specific and selective targeting of the genome, for the
* Anirban Basu [email protected] 1
Department of Chemistry, Vidyasagar University, Midnapore 721 102, India
2
CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India
treatment of many fatal genetic diseases using chemotherapeutic approaches (Waring 1981; Hurley 2002). Chelerythrine (1,2-dimethoxy-12-methyl[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium) (Fig. 1) is a benzophenanthridine alkaloid, close to sanguinarine, isolated from the natural herb, greater celandine Chelidonium majus L and Macleaya cordata. Sanguinarine, the close analogue, has received much at
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