Quinoline-3-Carboxylic Acids “DNA Minor Groove-Binding Agent”

Author(s):

Priyank Purohit*, Ravi K. Mittal and Kavita Khatana   Pages 344 - 348 ( 5 )

Abstract:

Background: The lead compounds from the series of 2, 4-disubstituted quinoline-3-carboxylic acid derivatives were selected for the <i>in-silico</i> mechanistic study. The compounds were found selective and potent for the cancer cell. Moreover, the relevant ADME <i>in-silico</i> data also support the safety of lead. <p> Objective: The objective of the study is to correlate the interaction of DNA and quinoline derivative, which was reported with the fluorescence microscopy images of cells <i>in-vitro</i> data in the recently published data. <p> Methods: The detailed interaction study with the DNA dodecanucleotide sequenced d(CGCGAATTCGCG) shows the present lead bounds with the A/T minor groove region of a B-DNA duplex through the important major and minor hydrogen bonds. <p> Results: The present <i>in-silico</i> study supports the interactions of the drug with DNA with sufficient binding interactions and energy. The present study also gives vital information related to the mechanism of drug action, which was initially declared as a DNA targeting molecule through a fluorescence-based target study. <p> Conclusion: The substitution at 2^nd position (the carbonyl group) of the lead revealed as a hydrogen bond donor/acceptor for adenine and guanine nucleic acid-base pair. The <i>in-silico</i> prediction also confirmed the interaction pattern of the lead with the DNA, which will be further utilized for drug development.

Keywords:

DNA interaction, minor groove binding agent, anti-cancer drug, quinoline, <i>in silico</i> interaction, heterocyclic moiety.

Affiliation:

Department of Pharmacy, HIMT, Gautam Budh Nagar, Greater Noida, Uttar Pradesh, 201308, , Department of Natural Product, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, SAS Nagar, Punjab-160062, cDepartment of chemistry, School of basic and applied sciences, SBAS, Galgotias University, Greater Noida. U.P

Graphical Abstract:

Read Full-Text article