title: Synthesis, spectroscopic characterization and in vitro antimicrobial, anticancer and antileishmanial activities as well interaction with Salmon sperm DNA of newly synthesized carboxylic acid derivative, 4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid.
abstract: This paper stresses on the synthesis, characterization of novel carboxylic acid derivative and its application in pharmaceutics. Carboxylic acid derivatives have a growing importance in medicine, particularly in oncology. A novel carboxylic acid, 4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid, was synthesized and characterized by elemental analysis, FT-IR, NMR ((1)H, and (13)C), mass spectrometry and single crystal X-ray structural analysis. The structure of the title compound, C11H12N2O6, shows the molecules dimerised by short intramolecular OH⋯O hydrogen bonds. The compound was screened for in vitro antimicrobial, anticancer, and antileishmanial activities as well as interaction with SS-DNA. The compound was also checked for in vitro anticancer activity against BHK-21, H-157 and HCEC cell lines, and showed significant anticancer activity. The compound was almost non-toxic towards human corneal epithelial cells (HCEC) and did not show more than 7.4% antiproliferative activity when used at the 2.0μg/mL end concentration. It was also tested for antileishmanial activity against the promastigote form of leishmania major and obtained attractive result. DNA interaction study exposes that the binding mode of the compound with SS-DNA is an intercalative as it results in hypochromism along with minor red shift. A new and efficient strategy to identify pharmacophores sites in carboxylic acid derivative for antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses was also carried out.
authors.affiliation: Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan; Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: m.siraj09@yahoo.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Sirajuddin
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address: drsa54@yahoo.com.
authors.forename: Saqib
authors.initials: S
authors.lastname: Ali
authors.affiliation: School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland.
authors.forename: Vickie
authors.initials: V
authors.lastname: McKee
authors.affiliation: Department of Chemistry, Hazara University, Mansehra, Pakistan.
authors.forename: Hameed
authors.initials: H
authors.lastname: Ullah
mesh_terms: D000813:Anilides / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism*; D005658:Fungi / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D008297:Male; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D066244:Proton Magnetic Resonance Spectroscopy; D012474:Salmon; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013094:Spermatozoa / Q000378:metabolism*; D013386:Succinates / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C000604099:4-(4-methoxy-2-nitrophenylamino)-4-oxobutanoic acid; D000813:Anilides; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D002264:Carboxylic Acids; D013386:Succinates; D004247:DNA
keywords: Anticancer activity; Antileishmanial activity; Antimicrobial activity; Carboxylic acid derivative; DNA interaction; Petra/Osiris/Molinspiration (POM) analyses