The Antioxidant and Antiproliferative Activities of 1,2,3-Triazolyl-L-Ascorbic Acid Derivatives

被引:16
|
作者
Harej, Anja [1 ]
Macan, Andrijana Mescic [2 ]
Stepanic, Visnja [3 ]
Klobucar, Marko [1 ]
Pavelic, Kresimir [4 ]
Pavelic, Sandra Kraljevic [1 ]
Raic-Malic, Silvana [2 ]
机构
[1] Univ Rijeka, Ctr High Throughput Technol, Dept Biotechnol, Radmile Matejcic 2, Rijeka 51000, Croatia
[2] Univ Zagreb, Fac Chem Engn & Technol, Dept Organ Chem, Marulicev Trg 20, Zagreb 10000, Croatia
[3] Rudjer Boskovic Inst, Div Elect, Bijenicka Cesta 54, Zagreb 10000, Croatia
[4] Juraj Dobrila Univ Pula, Fac Med, Zagrebacka 30, Pula 52100, Croatia
关键词
vitamin C; 1,2,3-triazole; antioxidant; quantum-chemical modelling; antitumor; HIF-1; HYPOXIA-INDUCIBLE FACTOR; FACTOR SIGNALING PATHWAYS; VITAMIN-C; NITRIC-OXIDE; FREE-RADICALS; OXIDATIVE STRESS; FREE-ENERGY; CANCER; HIF-1-ALPHA; ASCORBATE;
D O I
10.3390/ijms20194735
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The novel 4-substituted 1,2,3-triazole L-ascorbic acid (L-ASA) conjugates with hydroxyethylene spacer as well as their conformationally restricted 4,5-unsaturated analogues were synthesized as potential antioxidant and antiproliferative agents. An evaluation of the antioxidant activity of novel compounds showed that the majority of the 4,5-unsaturated L-ASA derivatives showed a better antioxidant activity compared to their saturated counterparts. m-Hydroxyphenyl (7j), p-pentylphenyl (7k) and 2-hydroxyethyl (7q) substituted 4,5-unsaturated 1,2,3-triazole L-ASA derivatives exhibited very efficient and rapid (within 5 min) 2,2-diphenyl-1-picrylhydrazyl (DPPH center dot) radical scavenging activity (7j, 7k: IC50 = 0.06 mM; 7q: IC50 = 0.07 mM). In vitro scavenging activity data were supported by in silico quantum-chemical modelling. Thermodynamic parameters for hydrogen-atom transfer and electron-transfer radical scavenging pathways of anions deprotonated at C2-OH or C3-OH groups of L-ASA fragments were calculated. The structure activity analysis (SAR) through principal component analysis indicated radical scavenging activity by the participation of OH group with favorable reaction parameters: the C3-OH group of saturated C4-C5(OH) derivatives and the C2-OH group of their unsaturated C4=C5 analogues. The antiproliferative evaluation showed that p-bromophenyl (4e: IC50 = 6.72 mu M) and p-pentylphenyl-substituted 1,2,3-triazole L-ASA conjugate (4k: IC50 = 26.91 mu M) had a selective cytotoxic effect on breast adenocarcinoma MCF-7 cells. Moreover, compound 4e did not inhibit the growth of foreskin fibroblasts (IC50 > 100 mu M). In MCF-7 cells treated with 4e, a significant increase of hydroxylated hypoxia-inducible transcription factor 1 alpha (HIF-1 alpha) expression and decreased expression of nitric oxide synthase 2 (NOS2) were observed, suggesting the involvement of 4e in the HIF-1 alpha signaling pathway for its strong growth-inhibition effect on MCF-7 cells.
引用
收藏
页数:26
相关论文
共 50 条
  • [21] HETEROCYCLES FROM CARBOHYDRATE PRECURSORS .4. PYRAZOLONE AND QUINOXALINE DERIVATIVES OF TRIAZOLYL ANALOGS OF L-ASCORBIC-ACID
    MOKHTAR, H
    SOLIMAN, R
    CARBOHYDRATE RESEARCH, 1981, 90 (01) : 144 - 148
  • [22] Synthesis, antibacterial activity, and CoMFA study of new 1,2,3-triazolyl 7-carboxamidodesacetoxy cephalosporanic acid derivatives
    Mohebbi, Maryam
    Salehi, Peyman
    Bararjanian, Morteza
    Aliahmadi, Atousa
    Safavi-Sohi, Reihaneh
    Ghasemi, Jahan B.
    MEDICINAL CHEMISTRY RESEARCH, 2014, 23 (10) : 4531 - 4541
  • [23] Synthesis, antibacterial activity, and CoMFA study of new 1,2,3-triazolyl 7-carboxamidodesacetoxy cephalosporanic acid derivatives
    Maryam Mohebbi
    Peyman Salehi
    Morteza Bararjanian
    Atousa Aliahmadi
    Reihaneh Safavi-Sohi
    Jahan B. Ghasemi
    Medicinal Chemistry Research, 2014, 23 : 4531 - 4541
  • [24] Experimental and theoretical evaluation of the anticorrosive proprieties of new 1,2,3-triazolyl-acridine derivatives
    Fernandes, Caio Machado
    Lessa, Renato C. S.
    Costa, Dora C. S.
    Guedes, Lucas
    Martins, Vinicius
    Al-Rashdi, Awad A.
    Ferreira, Vitor Francisco
    da Silva, Fernando de C.
    Silva, Julio Cesar M.
    de Moraes, Marcela C.
    Lgaz, Hassane
    Ponzio, Eduardo A.
    ARABIAN JOURNAL OF CHEMISTRY, 2024, 17 (01)
  • [25] L-ASCORBIC-ACID DERIVATIVES .2. SYNTHESIS OF DESOXY-L-ASCORBIC ACIDS
    DALLACKER, F
    SANDERS, J
    CHEMIKER-ZEITUNG, 1985, 109 (09): : 277 - 280
  • [26] Antioxidant and Antiproliferative Activities of Crossostephium chinensis (L.) Makino
    Chang, Tien-Ning
    Huang, Guan-Jhong
    Ho, Yu-Lin
    Huang, Shyh-Shyun
    Chang, Heng-Yuan
    Chang, Yuan-Shiun
    AMERICAN JOURNAL OF CHINESE MEDICINE, 2009, 37 (04): : 797 - 814
  • [27] Antioxidant and Antiproliferative Activities of Desmodium triflorum (L.) DC
    Lai, Shang-Chih
    Ho, Yu-Ling
    Huang, Shun-Chieh
    Huang, Tai-Hung
    Lai, Zhen-Rung
    Wu, Chi-Rei
    Lian, Kuo-Yuan
    Chang, Yuan-Shiun
    AMERICAN JOURNAL OF CHINESE MEDICINE, 2010, 38 (02): : 329 - 342
  • [28] Exploring the antioxidant potential of bis-1,2,3-triazolyl-N-phenylacetamides
    Deshmukh, Tejshri R.
    Khedkar, Vijay M.
    Sangshetti, Jaiprakash N.
    Shingate, Bapurao B.
    RESEARCH ON CHEMICAL INTERMEDIATES, 2023, 49 (02) : 635 - 653
  • [29] Exploring the antioxidant potential of bis-1,2,3-triazolyl-N-phenylacetamides
    Tejshri R. Deshmukh
    Vijay M. Khedkar
    Jaiprakash N. Sangshetti
    Bapurao B. Shingate
    Research on Chemical Intermediates, 2023, 49 : 635 - 653
  • [30] Aminodiols, aminotetraols and 1,2,3-triazoles based on allo-gibberic acid: stereoselective syntheses and antiproliferative activities
    Khdar, Zein Alabdeen
    Le, Tam Minh
    Schelz, Zsuzsanna
    Zupko, Istvan
    Szakonyi, Zsolt
    RSC ADVANCES, 2024, 14 (49) : 36698 - 36712