Xanthone Conjugated Amino Acids as Potential Anticancer and DNA Binding Agents: Molecular Docking, Cytotoxicity and SAR Studies

Title:Xanthone Conjugated Amino Acids as Potential Anticancer and DNA Binding Agents: Molecular Docking, Cytotoxicity and SAR Studies

Volume: 18 Issue: 15

Author(s): Kadallipura P. Rakesh, Nanjudappa Darshini, Honnayakanakalli M. Manukumar, Hamse K. Vivek, Mohammed Y.H. Eissa, Doddakunche S. Prasanna*Ningegowda Mallesha*

Affiliation:

• Department of Nanotechnology, Visvesvaraya Technological University, Bengaluru Region, Muddenahalli, Chikkaballapur - 562 101,India

• Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, 205 Luoshi Road, Wuhan, 430070,China

Keywords: Xanthone, amino acids, anticancer, SAR, docking, doxorubicin, binding interactions, structure-activity relationship.

Abstract: Background: Amino acids conjugated with heterocyclic molecules are well known for their effective bioactive properties. In search of effective anticancer agents, a series of xanthone linked amino acids 2-23 were synthesized and tested for in vitro anticancer activity.

Methods: In vitro anticancer activity of the synthesized xanthone linked amino acids 2-23 are tested against three different cancer cell lines MCF-7, MDA-MB-435 and A549 by MTT assay and validated by DNA binding and molecular docking approaches. Doxorubicin and ethidium bromide used as standard and positive control respectively.

Results: Compounds 7, 8 and 9 exhibited potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green. In the molecular docking study, binding interactions of the most active compounds 7, 8 and 9 were confirmed to molecular surface of DNA.

Conclusion: Structure-Activity Relationship (SAR) showed that the aromatic and hydrophobic amino acids (phenylalanine, tyrosine, and tryptophan) favoured the DNA binding studies and anticancer activity whereas, aliphatic amino acids showed least anticancer activity.

Cite this article as:

Rakesh P. Kadallipura, Darshini Nanjudappa, Manukumar M. Honnayakanakalli, Vivek K. Hamse, Eissa Y.H. Mohammed , Prasanna S. Doddakunche*, Mallesha Ningegowda*, Xanthone Conjugated Amino Acids as Potential Anticancer and DNA Binding Agents: Molecular Docking, Cytotoxicity and SAR Studies, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (15) . https://dx.doi.org/10.2174/1871520618666180903105256