Investigation of DNA binding and molecular docking propensity of phthalimide derivatives: in vitro antibacterial and antioxidant assay

Arif et al. Journal of Analytical Science and Technology https://doi.org/10.1186/s40543-019-0177-1 (2019) 10:19 Journal of Analytical Science and Technology RESEARCH ARTICLE Open Access Investigation of DNA binding and molecular docking propensity of phthalimide derivatives: in vitro antibacterial and antioxidant assay Rizwan Arif1, Pattan Sirajuddin Nayab1, Akrema1, Mohammad Abid2, Umesh Yadava3 and Rahisuddin1* Abstract A series of N-substituted tetrabromphthalimide derivatives was synthesized by condensation reaction using tetrabromophthalic anhydride with 3,5-diamino-1,2,4-triazole/ 2,6-diaminopyridine/ 2,6-diamino-4-hydroxy pyrimidine/ o-tolidine. All the synthesized phthalimide derivatives were characterized by elemental analysis, infrared, and NMR spectroscopy. In vitro antibacterial evaluation was carried out for the synthesized compounds. Results revealed that compound 1 showed potential activity against Escherichia coli (100 μg/mL) and Streptococcus mutans (150 μg/mL). On the basis of antibacterial activity, compound 1 was selected for DNA binding interaction, though DNA target most of the antibacterial drugs. The DNA binding modes of the compound 1 with Ct-DNA (calf thymus) were studied by absorption measurements, hydrodynamic measurements and cyclic voltammetry methods. Molecular docking also confirms that compound 1 recognizes both the strands of the DNA dodecamer d(CGCGAATTC GCG)2 within minor groove and showing the best binding capability with the duplex. Compound 1 also showed better antioxidant activity by 2,2-diphenyl-1-picryl-hydrazyl (DPPH) free radical and hydrogen peroxide. Keywords: Phthalimide, Antibacterial, Antioxidant, DNA, DPPH Introduction Heterocyclic phthalimides are well explored derivatives among important class of pharmacophores for the preparation of variety of drugs because of its similar structural properties (hydrophobic aryl ring and an electrondonating group), they possess variety of important biological activities. Due to its wide range of applications in medicinal chemistry and pharmaceutics (Bhat and Al-Omar 2011; Mohamed et al. 2015) viz. antibacterial (Lohan et al. 2014; Silva et al. 2014; Zhang et al. 2015), antifungal, anti-inflammatory (Buddana et al. 2015; Al-Qaisi et al. 2014), antivirus (Shi et al. 2011), antagonistic (Lin et al. 2009), and anti-androgens (Roy et al. 2007), it is an important and tremendous subject for today’s research. Apart from their pharmaceutical applications, phthalimide also serves as herbicides (Balachandran et al. 2012), used in production of pesticides (Wang et al. * Correspondence: 1 Department of Chemistry, Jamia Millia Islamia, New Delhi 110025, India Full list of author information is available at the end of the article 2013) and dyes (Choi et al. 2010). They were also found with industrial applications as bleaching agent, heat-resistant polymer, and flame retardants (Krishnakumar et al. 2005). For the amine protection in organic synthesis, phthalimide moiety is an important constituent. In the process of production, the knowledge of thermodynamic parameters or solvent crystallization is significant and process for purifying the phthalimide derivatives by virtue of crystallization method induces by the awareness of their solubility in appropriate solvent system. Li and his co-workers determine the solubility of various phthalimide derivatives experimentally by using the isothermal dissolution equilibrium method in mixed solvent systems (Li et al. 2017). Phthalimide derivatives exhibited various biological activities and proved as a noteworthy pharmacophore and can interact with the peripheral anionic site of the enzyme. A series of phthalimide derivatives was synthesized as multi-function inhibitors for the treatment of Alzheimer’s disease (AD) © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. (2019) 10:19 Page 2 of 9 and found to be a balanced multi-target active molecule which exhibited potent and balanced inhibitory activities against cholinesterase inhibitors (Sang et al. 2017). Due to industrial development and high requirement, phthalimide was prepared on a large scale by various methods in high yield. Due to very low solubility in water, separation of phthalimide is not easy. Hence to rectify these problems, many methods have been developed by the researchers for the separation and purification of phthalimides in high yield (Kushwaha and Kaushik 2016). Heterocyclic phthalimide derivatives are very much useful for the construction of macromolecules, in supramolecular chemistry, useful in catalytic reaction and photochemistry (Yoon et al. 1997; Cho et al. 2010). A series of polyester derived from phthalimide, which are thermally stable and highly soluble in polar solvents, has been also reported (Behniafar et al. 2015). DNA plays major role in many physiological and biological processes. Various targeting drugs for DNA which was approved as significant antimicrobial agents currently available in the market but due to their side effects and highly clinical costs, many researchers are working on developing new antimicrobial drugs. The biological activity of the antibacterial drugs containing heterocyclic ring is due to inhibition of DNA replication (Nayab et al. 2015a, b, 2016). In view of these prospective, the study of DNA interaction with phthalimides has been considered a subject of great importance for the investigation of potential antimicrobial and anticancer drugs and molecular docking technique can be used for knowing the aspect of intermolecular interactions of proteins and ligands. Considering these facts, in the current research work, we have synthesized tetrabromo phthalimide derivatives by the condensation reaction of tetrabromo phthalic anhydride and 3,5-diamino-1,2,4-triazole/ 2,6-diaminopyridine/ 2,6-diamino-4-hydroxy pyrimidine/ o-tolidine in order to prepare potent antibacterial and DNA binding agents. recorded on Perkin Elmer Lamda 40 UV-visible spectrophotometer. IR spectra were recorded on Agilent Cary 630 FTIR spectrometer as neat sample. 1H NMR spectra were recorded on Bruker DPX-300 NMR spectrometer operating at 400 MHz using DMSO-d6 as solvent with TMS as internal standard. Chemical shift values are given in ppm. Cyclic voltammetric measurements were performed by using DY2312 potentiostat. The antibacterial experiment was performed against Streptococcus mutans (MTCC 3224), and Escherichia coli (ATCC 25922) bacterial strains. To perform molecular docking study Gaussian 03 software was used. The antioxidant potential of the phthalimide derivatives was also estimated using DPPH (...truncated)