Copyright@ Abdul M Gbaj | Biomed J Sci & Tech Res | BJSTR. MS.ID.004062. 18318 Research Article ISSN: 2574 -1241 Virtual Screening of Phenylenediamine Schiff`s Base Derivatives as Possible DNA Intercalating Agents Nisreen H Meiqal 1 , Bushra E Ammar 1 , Inass A Sadawe 1 , Abdulathim A A Alshoushan 2 , Salah M Bensaber 1 , Omran Fhid 1 , Anton Hermann 3 and Abdul M Gbaj 1 * 1 Department of Medicinal Chemistry, Faculty of Pharmacy, University of Tripoli, Libya 2 National Centre for Food and Drug Control (LFDA), Tripoli, Libya 3 Department of Biosciences, University of Salzburg, Salzburg, Austria *Corresponding author: Abdul M Gbaj, Department of Medicinal Chemistry, Faculty of Pharmacy, University of Tripoli, Libya DOI: 10.26717/BJSTR.2020.24.004062 Introduction There are several ways by which organic compounds can interact with Deoxyribonucleic Acid (DNA), including covalent bonding, electrostatic binding or intercalation. Intercalation occurs when the compound (ligand) of appropriate size and chemical nature fit between base pairs of DNAs [1,2]. In order for an intercalator to fit between base pairs, they must consist of planar polycyclic aromatic rings, and the DNA must dynamically open a space between its base pairs by unwinding [3]. The ability of intercalating agents to inhibit DNA replication and nucleic acid synthesis in vivo leads to their extensive use as mutagens, antibiotics, antibacterials, trypanocides, schistosomicides, and antitumor agents. The intercalative binding is non-covalent stacking interaction resulting from the insertion of a planar aromatic ring(s) between the base pairs of the DNA double helix [4,5]. Many classes of organic compounds have been reported to possess good DNA intercalating activity. Among these agents, Schiff’s bases (imines) showed a large range of biological activities including antiviral, antibacterial, antiproliferative, antifungal, and antimalarial activities [6-8]. Received: December 30, 2019 Published: January 10, 2020 Citation: Nisreen H Meiqal, Bushra E Ammar, Inass A Sadawe, Abdulathim A A Alshoushan, Salah M Bensaber, Omran Fhid, Anton Hermann, Abdul M Gbaj. Virtual Screening of Phenylenediamine Schiff`s Base Derivatives as Possible DNA Intercalating Agents. Biomed J Sci & Tech Res 24(3)-2020. BJSTR. MS.ID.004062. Keywords: Schiff`s Base; Phenylenedi- amine; Dna Intercalation; Molecular Dock- ing; Bioactivity; Antibiotic ARTICLE INFO Abstract Several Schiff’s base derivatives for the three structural isomers of phenylenedi- amine have been designed and evaluated for their DNA intercalation ability. ADMET properties and drug-likeliness of the investigated compounds were predicted by swis- sADME software. The starting geometry of each investigated compound was construct- ed using chem3D Ultra software. Molecular docking studies for the intercalation of all compounds with DNA were performed using PyRx software based on Vina as docking software and Lamrkian genetic algorithm as scoring function. The three isomers of phe- nylenediamine (ortho, meta and para) were used to design the investigated Schiff’s base derivatives, which were divided into several groups (A-G) within two series. Our dock- ings result of the first series revealed the importance of meta phenylenediamine deriva- tives over the other (ortho and para) isomers. In addition, they showed the vital role of the naphthyl ring as an aromatic side chain especially when it has a hydroxyl substituent at position 2 of the naphthyl ring. Series 2 contains 4 groups (D-G), and their docking results indicate the importance of another substituent (nitro, methyl, isopropyl, chloro) at position 4 of the aromatic ring. Two main modifications have led to good binding affinities at the DNA intercalatingsite. The first modification involved the use of three ring systems (anthracene or phenanthrene), while the second modification connects the aromatic ring via position 2 instead position 1of the substituted aromatic ring. In conclusion, we have successfully designed several symmetrical meta phenylenediamine Schiff`s bases which can be easily synthesized and used as DNA intercalators. Among all the studied compounds, the derivative which has a hydroxyl anthracene ring connected via position 2 to the meta isomer of phenylenediamine (compound BNG702) showed the highest DNA binding affinity.