title: Structure elucidation, DNA binding specificity and antiproliferative proficiency of isolated compounds from Garcinia nervosa.
abstract: Garcinia nervosa is an abundant source of bioactive phytochemicals. The present paper deals with the isolation of a novel isoflavone 5,7-dihydroxy-3-(3'-hydroxy-4',5'-dimethoxyphenyl)-6-methoxy-4H-chromen-4-one (1) along with a known compound DL-Allantoin (2) from the ethanolic extract of the leaves of Garcinia nervosa (Family: Guttiferae). Their structures were elucidated on the basis of chemical and physical evidences viz. elemental analysis, UV, FT-IR,1H NMR,13C NMR and mass spectral analysis. Single-crystal X-ray analysis was further used for the authentication of structure of both compounds (1 and 2). Interaction studies of compound (1) and (2) with ctDNA were studied by UV-Visible spectroscopy, fluorescence, KI quenching studies, competitive displacement assay and circular dichroism studies, which showed groove binding interaction (non-intercalation) of both the compounds 1 and 2 with ctDNA. However, compound 1 (K=3.9×104M-1) shows higher binding affinity to the ctDNA than compound 2 (K=1.44×104M-1). The molecular modeling results also illustrated that compound 1 strongly binds to groove of DNA by relative binding energy of docked structure -6.82kcal/mol. In addition the antiproliferative activity also showed high potential of compound 1 against MCF-7 and MDA-MB 231 cell line with IC50value 8.44±3.5μM and 6.94±2.6μM, respectively.
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India. Electronic address: mehtab.organic2009@gmail.com.
authors.forename: Mehtab
authors.initials: M
authors.lastname: Parveen
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Shaista
authors.initials: S
authors.lastname: Azaz
authors.affiliation: Department of Biochemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Atif
authors.initials: A
authors.lastname: Zafar
authors.affiliation: Department of Chemistry, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Faheem
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: CEMDRX Physics Department, University of Coimbra, 3004-516 Coimbra, Portugal.
authors.forename: Manuela Ramos
authors.initials: MR
authors.lastname: Silva
authors.affiliation: CEMDRX Physics Department, University of Coimbra, 3004-516 Coimbra, Portugal.
authors.forename: Pedro Sidonio Pereira
authors.initials: PS
authors.lastname: Silva
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D029760:Garcinia / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D010936:Plant Extracts / Q000494:pharmacology*; D013057:Spectrum Analysis
chemical_list: D010936:Plant Extracts; D004247:DNA
keywords: Antiproliferative activity; DNA binding study; Garcinia nervosa; Isoflavone; X-ray analysis