title: Synthesis and evaluation of resveratrol derivatives as new chemical entities for cancer.
abstract: Resveratrol has been shown to be active in inhibiting multistage carcinogenesis. The potential use of resveratrol in cancer chemoprevention or chemotherapy settings has been hindered by its short half-life and low bioavailability. Considering the above remarks, using resveratrol as a prototype, we have synthesized two derivatives of resveratrol. Their activity was evaluated using in vitro and in silico analysis. Biological evaluation of resveratrol analogues on U937 cells had shown that two synthesized analogues of resveratrol had higher rates of inhibition than the parental molecule at 10μM concentration. EMSA conducted for NF-kB revealed that these molecules significantly interfered in the DNA binding ability of NF-kB. It was found that these molecules suppressed the expression of TNFα, TNFR, IL-8, actin and activated the expression of FasL, FasR genes. To understand possible molecular mechanism of the action we performed docking and dynamic studies, using NF-kB as a receptor. Results showed that resveratrol, RA1 and RA2 interacted with the residues involved in DNA binding. Resveratrol analogues by interacting NF-kB might have prevented its translocation and also by interacting with the residues involved in DNA binding might have prevented the binding of NF-kB to DNA. This may be the reason for suppression of NF-kB binding to DNA.
authors.affiliation: Department of Biochemistry, Sri Krishandevaraya University, Anantapur 515003, A.P., India.
authors.forename: Chaitanya
authors.initials: C
authors.lastname: Mulakayala
authors.forename: B
authors.initials: B
authors.lastname: Babajan
authors.forename: P
authors.initials: P
authors.lastname: Madhusudana
authors.forename: C M
authors.initials: CM
authors.lastname: Anuradha
authors.forename: Raja Mohan
authors.initials: RM
authors.lastname: Rao
authors.forename: Ravi Prakash
authors.initials: RP
authors.lastname: Nune
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Manna
authors.forename: Naveen
authors.initials: N
authors.lastname: Mulakayala
authors.forename: Chitta Suresh
authors.initials: CS
authors.lastname: Kumar
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000378:metabolism; 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 / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000138:chemical synthesis* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; 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; D000077185:Resveratrol