title: Natural and Synthetic Flavonoids: Structure-Activity Relationship and Chemotherapeutic Potential for the Treatment of Leukemia.
abstract: Flavonoids and their derivatives are polyphenolic secondary metabolites with an extensive spectrum of pharmacological activities, including antioxidants, antitumor, anti-inflammatory, and antiviral activities. These flavonoids can also act as chemopreventive agents by their interaction with different proteins and can play a vital role in chemotherapy, suggesting a positive correlation between a lower risk of cancer and a flavonoid-rich diet. These agents interfere with the main hallmarks of cancer by various individual mechanisms, such as inhibition of cell growth and proliferation by arresting the cell cycle, induction of apoptosis and differentiation, or a combination of these mechanisms. This review is an effort to highlight the therapeutic potential of natural and synthetic flavonoids as anticancer agents in leukemia treatment with respect to the structure-activity relationship (SAR) and their molecular mechanisms. Induction of cell death mechanisms, production of reactive oxygen species, and drug resistance mechanisms, including p-glycoprotein efflux, are among the best-described effects triggered by the flavonoid polyphenol family.
authors.affiliation: a Department of Chemistry & QOPNA , University of Aveiro , Aveiro , Portugal.
authors.forename: José C J M D S
authors.initials: JC
authors.lastname: Menezes
authors.affiliation: b Department of Pharmacy , College of Pharmacy, Seoul National University , Gwanak-gu, Seoul , South Korea.|c Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg , Luxembourg , Luxembourg.
authors.forename: Barbora
authors.initials: B
authors.lastname: Orlikova
authors.affiliation: c Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Fondation de Recherche Cancer et Sang, Hôpital Kirchberg , Luxembourg , Luxembourg.
authors.forename: Franck
authors.initials: F
authors.lastname: Morceau
authors.affiliation: b Department of Pharmacy , College of Pharmacy, Seoul National University , Gwanak-gu, Seoul , South Korea.
authors.forename: Marc
authors.initials: M
authors.lastname: Diederich
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D004032:Diet; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D005419:Flavonoids
keywords: Flavonoids; P-glycoprotein; PARP; ROS; SAR; apoptosis; caspase; chemoprevention; cytotoxic; leukemia; mitochondria