title: Experimental and computational studies on newly synthesized resveratrol derivative: a new method for cancer chemoprevention and therapeutics?
abstract: Nature has been a provenance of medicinal agents for thousands of years. Resveratrol (RESL) is a naturally occurring polyphenolic compound in food stuffs such as peanuts, seeds, berries, grapes, and beverages (red wine). RESL has received significant attention due to a plethora of in vitro and in vivo reports on its cancer chemopreventive and therapeutic properties. In the present study, diacetate RESL derivative (RESL43) was synthesized. The RESL43 displayed potent cytotoxicity and triggered apoptosis in U937 cells as evidenced by poly (ADP-ribose) polymerase (PARP) cleavage, DNA fragmentation, morphological changes, and activation of FasR and FasL genes. The electrophoretic mobility shift assay revealed the suppression NFkB activity in U937 cells after treatment with RESL43 in corroboration with the deactivation of NFkB dependent genes such as IL-8, TNFR, and TNFα. Furthermore, molecular docking and dynamics studies have shown that RESL and RESL43 might exert their inhibitory activity on NFkB by altering the intramolecular binding abilities between DNA and NFkB. Taken together, RESL43 can have greater putative activity than parental RESL in a context of cancer chemoprevention and therapeutics. We suggest that the diacetate resveratrol derivative RESL43 warrants further evaluation in preclinical and clinical bridging studies in the near future.
authors.affiliation: 1 DBT-Bioinformatics Infrastructure Facility, Department of Biochemistry, Sri Krishnadevaraya University , Anantapur, India .
authors.forename: Babajan
authors.initials: B
authors.lastname: Banaganapalli
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Mulakayala
authors.forename: Madhusudana
authors.initials: M
authors.lastname: Pulaganti
authors.forename: Naveen
authors.initials: N
authors.lastname: Mulakayala
authors.forename: C M
authors.initials: CM
authors.lastname: Anuradha
authors.forename: Chitta
authors.initials: C
authors.lastname: Suresh Kumar
authors.forename: Noor Ahmad
authors.initials: NA
authors.lastname: Shaik
authors.forename: Jumana
authors.initials: J
authors.lastname: Yousuf Al-Aama
authors.forename: Dhananjaya
authors.initials: D
authors.lastname: Gudla
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D053938:DNA Fragmentation; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D062105:Molecular Docking Simulation; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000517:prevention & control; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D016209:Interleukin-8; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D000077185:Resveratrol