title: 1,2,3,4,6-Pentakis[-O-(3,4,5-trihydroxybenzoyl)]-α,β-D-glucopyranose (PGG) analogs: design, synthesis, anti-tumor and anti-oxidant activities.
abstract: 1,2,3,4,6-Pentakis[-O-(3,4,5-trihydroxybenzoyl)]-α,β-D-glucopyranose (PGG) 12 has been reported for its antioxidant activities, where the free OH groups in PGG seem to be critical for activities. To explore PGG-based compounds as chemotherapeutic agents and to analyze the contribution of specific OH groups in PGG for anti-cancer activities, we designed and synthesized a series of 27 benzoic and cinnamic acid analogs of PGG. These analogs were tested for cytotoxicities against two human lung (A549 and H1299) and two human colon (HCT116 and HT29) cancer cell lines. Compound 12 (PGG) had highest cytotoxicities against HCT116 and A549 cells with IC50 of 1.61 µM and 3.02 µM, respectively. In contrast, the compound 16 (1,2,3,4,6-pentakis[-O-(4-hydroxy-3-methoxybenzoyl)]-α,β-D-glucopyranose, PVG) was most effective at killing HT29 and H1299 cells with IC50 of 1.76 µM and 3.65 µM, respectively, indicating the mutual contribution of m-methoxy and p-hydroxy groups to the observed cytotoxicities. Moreover, cinnamic acid analogs were less active than the benzoic acid analogs evidenced by higher IC50 values. Furthermore, in cinnamic acid analogs the hydrogenation of double bond to saturated 2-C side chain enhance the cytotoxicities in all four cell lines. Compounds also possess good anti-oxidant and reducing activities. Compound 12 and 26 show the highest antioxidant and reducing activities.
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, China.
authors.forename: Qurat-Ul-Ain
authors.initials: QU
authors.lastname: Shaikh
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, China.
authors.forename: Meiting
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Zoology, Shah Abdul Latif University, Pakistan.
authors.forename: Khadim Hussain
authors.initials: KH
authors.lastname: Memon
authors.affiliation: Multidisciplinary laboratory, Medical and Dental College, Bahria University Karachi, Pakistan.
authors.forename: Mehreen
authors.initials: M
authors.lastname: Lateef
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, China.
authors.forename: Du
authors.initials: D
authors.lastname: Na
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, China.
authors.forename: Shengbiao
authors.initials: S
authors.lastname: Wan
authors.affiliation: European Institute for Marines Studies, University of Western Brittany, France.
authors.forename: Deslandes
authors.initials: D
authors.lastname: Eric
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, China. Electronic address: lijuanzhang@ouc.edu.cn.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, China. Electronic address: jiangtao@ouc.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000737:chemistry; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005947:Glucose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000737:chemistry; D010851:Picrates / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D010851:Picrates; C105369:Y-ART 3; D005707:Gallic Acid; C004931:1,1-diphenyl-2-picrylhydrazyl; D007501:Iron; D005947:Glucose
keywords: Anti-tumor; Inhibition; Pentagalloylglucose (PGG); Pentavanilloylglucose (PVG)