title: Natural polyphenolic inhibitors against the antiapoptotic BCL-2.
abstract: The apoptotic mechanism is regulated by the BCL-2 family of proteins, such as BCL-2 or Bcl-xL, which block apoptosis while Bad, Bak, Bax, Bid, Bim or Hrk induce apoptosis. The overexpression of BCL-2 was found to be related to the progression of cancer and also providing resistance towards chemotherapeutic treatments. In the present study, we found that all polyphenols (apigenin, fisetin, galangin and luteolin) bind to the hydrophobic groove of BCL-2 and the interaction is stable throughout MD simulation run. Luteolin was found to bind with highest negative binding energy and thus, claimed highest potency towards BCL-2 inhibition followed by fisetin. The hydrophobic interactions were found to be critical for stable complex formation as revealed by the vdW energy and ligplot analysis. Finally, on the basis of data obtained during the study, it can be concluded that these polyphenols have the potential to be used as lead molecules for BCL-2 inhibition.
authors.affiliation: a School of Biotechnology , Jawaharlal Nehru University , New Delhi , India.
authors.forename: Sharad
authors.initials: S
authors.lastname: Verma
authors.affiliation: b Department of Biotechnology , TERI University , Vasant Kunj , New Delhi , India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Singh
authors.affiliation: b Department of Biotechnology , TERI University , Vasant Kunj , New Delhi , India.
authors.forename: Anchala
authors.initials: A
authors.lastname: Kumari
authors.affiliation: a School of Biotechnology , Jawaharlal Nehru University , New Delhi , India.
authors.forename: Chetna
authors.initials: C
authors.lastname: Tyagi
authors.affiliation: c Department of Bioscience and Biotechnology , Banasthali University , Tonk , Rajasthan , India.
authors.forename: Sukriti
authors.initials: S
authors.lastname: Goyal
authors.affiliation: c Department of Bioscience and Biotechnology , Banasthali University , Tonk , Rajasthan , India.
authors.forename: Salma
authors.initials: S
authors.lastname: Jamal
authors.affiliation: a School of Biotechnology , Jawaharlal Nehru University , New Delhi , India.
authors.forename: Abhinav
authors.initials: A
authors.lastname: Grover
mesh_terms: D047310:Apigenin / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry* / Q000235:genetics; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D044948:Flavonols; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology; D059808:Polyphenols / Q000737:chemistry* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D005419:Flavonoids; D044948:Flavonols; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2; C037032:galangin; D047310:Apigenin; D047311:Luteolin; C017875:fisetin
keywords: BCL-2; free energy calculation; molecular docking; molecular dynamics simulation; polyphenols; principal component analysis