Journal of Applied Biological Chemistry

The Korean Society for Applied Biological Chemistry (한국응용생명화학회)
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The Influence of the Substituents on the Benzo Ring for Antioxidant Activity of 4-Methyl-2H-benzopyran-2-one Analogues

4-Methyl-2H-benzopyran-2-one 유도체들의 항산화 활성에 관한 Benzo 고리상 치환기들의 영향

  • Choi, Won-Seok (Department of Applied Biology & Chemistry, College of Agriculture & Life Sciences, Chungnam National University) ;
  • Lee, Jae-Whang (Department of Applied Biology & Chemistry, College of Agriculture & Life Sciences, Chungnam National University) ;
  • Cho, Yun-Gi (Department of Applied Biology & Chemistry, College of Agriculture & Life Sciences, Chungnam National University) ;
  • Sung, Nack-Do (Department of Applied Biology & Chemistry, College of Agriculture & Life Sciences, Chungnam National University)
  • 최원석 (충남대학교 농업생명과학대학 응용생물화학과) ;
  • 이재황 (충남대학교 농업생명과학대학 응용생물화학과) ;
  • 조윤기 (충남대학교 농업생명과학대학 응용생물화학과) ;
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학과)
  • Received : 2010.02.24
  • Accepted : 2010.04.16
  • Published : 2010.06.30
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Abstract

The influences on antioxidant activities of the substituents ($R_1-R_4$) on benzo ring in 4-Methyl-2H-benzopyran-2-one analogues (1-23) were discussed quantitatively using three dimensional quantitative structure-activity relationships (3D-QSARs: Comparative molecular field analyses (CoMFA) and Comparative molecular similarity indice analyses (CoMSIA)) methods. The statistical qualities of CoMSIA models were better than those of CoMFA models and the CoMSIA 2 model was optimized model ($q^2$=0.700 & $r^2$=0.979). Also, the contribution ratios (%) of the optimized CoMSIA 2 model were H-bond donor field 43.5%, electrostatic field 41.8% and steric field 14.7% so that the antioxidant activity exhibited a strong correlation with H-bond donor and electrostatic factor of molecules. From the analytical results of the CoMSIA contour maps, if the positive charge favor group and H-bond donor disfavor group were placed in the $R_1-R_4$ positions on the benzo ring, it was predicted that the groups would raised the antioxidant activity.

3차원적인 정량적 구조-활성상관(3D-QSAR: 비교분자 유사성지수분석(CoMSIA) 및 비교분자장분석(CoMFA)) 기법에 기초하여 4-Methyl-2H-benzopyran-2-one 유도체들(1-23)의 항산화활성에 관한 benzo 고리상 치환기($R_1-R_4$)들의 영향을 정량적으로 검토하였다. CoMSIA 모델은 CoMFA 모델보다 통계적으로 양호하였으며 최적화된 CoMSIA 2 모델의 예측성($q^2$=0.700)과 상관성($r^2$=0.979)이 가장 양호하였다. 항산화 활성에 관한 CoMSIA 2 모델의 기여비율(%)은 수소결합 주게장(HD) 43.5%, 정전기장(E) 41.8% 및 입체장(S) 14.7%로 정전기장과 H-결합 주게장이 항산화활성에 가장 큰 영향을 미치는 요소이었다. CoMSIA 등고도 분석결과, benzo 고리상에 양하전을 선호하며, 그리고 H-결합주게가 아닌 치환기($R_1-R_4$)들이 항산화활성을 증가시킬 것으로 예상되었다.

Keywords

References

  1. Adeline B, Rodriguez D, Gilbert K and Denyse B (2008) Synthesis and protective effects of coumarin derivatives against oxidative stress induced by doxorubicin. Bioorg Med Chem Lett 18, 1102-1105. https://doi.org/10.1016/j.bmcl.2007.12.004
  2. Appendino G, Mercalli E, Fuzzati N, Arnoldi L, Stavri M, Gibbons S, Ballero M and Maxia A (2004) Antimycobacterial coumarins from the sardinian giant fennel. J Nat Prod 67, 2108-2110. https://doi.org/10.1021/np049706n
  3. Bedoya LM, Beltran M, Sancho R, Olmedo DA, Sanchez PS, Olmo E, Lopez-Perez JL, Munoz E, San FA and Alcami J (2005) 4-Phenylcoumarins as HIV transcription inhibitors. Bioorg Med Chem Lett 15, 4447-4450. https://doi.org/10.1016/j.bmcl.2005.07.041
  4. Bynum JB, Cothren JT, Lemon RG, Fromme D and Boman RK. (2007) Field Evaluation of Nitrophenolate plant growth regulator (Chaperone) for the effect on cotton lint yield. J Cotton Sci 11, 20-25.
  5. Cakici H, Esenpinar AA and Bulut M. (2008) Synthesis and characterization of novel phthalocyanines bearing quaternizable coumarin. Polyhedron 27, 3625-3630. https://doi.org/10.1016/j.poly.2008.09.016
  6. Cavar S, Kovac F and Marsimovic M. (2009) Synthesis and antioxidant activity of selected 4-methylcoumarins. Food Chem 117, 135-142. https://doi.org/10.1016/j.foodchem.2009.03.087
  7. Chang YC, Lee FW, Chen CS, Huang ST, Tsai SH, Huang SH and Lin CM (2007) Structure-activity relationship of C6-C3 phenylpropanoids on xanthine oxidase- inhibiting and free radical-scavenging activities. Free Radical Bio Med 43, 1541-1551. https://doi.org/10.1016/j.freeradbiomed.2007.08.018
  8. Ghate M, Manohar D, Kulkarni V, Shobha R and Kattimani SY (2003) Synthesis of vanillin ethers from 4-(bromomethyl) coumarins as anti-inflammatory agents. Eur J Med Chem 38, 297-302. https://doi.org/10.1016/S0223-5234(03)00016-3
  9. Ito C, Itoigawa M, Mishina Y, Filho VC., Enjo H, Tokuta H, Nishino H and Hurukawa H (2003) Chemical constituents of Calophyllum brasiliense. 2. Structure of three new coumarins and cancer chemopreventive activity of 4-substituted coumarins. J Nat Prod 66, 368-371 https://doi.org/10.1021/np0203640
  10. Khan KM, Iqbal S, Lodhi MA, Maharvi GM, Perveen S, Choudhary MI, Atta UR, Chohan ZH and Supuran CT (2004) Synthesis and urease enzyme inhibitory effects of some dicoumarols. J Enzym Inhib Med Chem 19, 367-371. https://doi.org/10.1080/14756360409162452
  11. Kidane A, G, Henryk S, Alok T, K, Richard B and Alexander M (2004) Anticoagulant and antiplatelet agents: Their clinical and device applications together with usages to engineer surfaces. Biomacromolecules 5, 798-813. https://doi.org/10.1021/bm0344553
  12. Klebe G, Abraham U and Mietzner T (1994) Molecular similarity indexes in a comparative- analysis (comsia) of drug molecules to correlate and predict their biological-activity. J Med Chem 37, 4130-4146. https://doi.org/10.1021/jm00050a010
  13. Kliner HE, Xia X, Sonoda J, Zhang J, Pontius E, Abey J, Evans R, M., Moore D and Digiovanni J (2008) Effects of naturally occurring coumarins on hepatic drug-metabolizing enzymes in mice. Toxicol Appl Pharm 232, 337-350. https://doi.org/10.1016/j.taap.2008.07.004
  14. Kontogiorgis CA and Hadjipavlou DJ (2004) Synthesis and biological evaluation of novel coumarin derivatives with a 7- azomethine linkage. Bioorg Med Chem Lett 14, 611-614. https://doi.org/10.1016/j.bmcl.2003.11.060
  15. Lorenz P, Zeh M, Martens-Lobenhoffer J, Schmidt H, Wolf G and Horn T (2005) Natural and newly synthesized hydroxy-1-arylisochromans: A clas of potential antioxidants and radical scavengers. Free Radical Res 39, 535-545. https://doi.org/10.1080/10715760500073733
  16. Martin YC (1998) 3D-QSAR: Current state, scope, and limitations. Perspectives in Drug Discov Des 12, 3-23. https://doi.org/10.1023/A:1017037831628
  17. Melagraki G, Afantitis A, Igglessi-Markopoulou O, Detsi A, Koufaki M, Kontogiorgis C and Hadjipavlou-Litina DJ (2009) Synthesis and evaluation of the antioxidant and antiinflammatory activity of novel coumarin-3-aminoamides and their alpha-lipoic acid adducts. Eur J Med Chem 44, 3020- 3026. https://doi.org/10.1016/j.ejmech.2008.12.027
  18. Nishikawa M, Hashida M and Takakura Y. (2009) Catalase delivery for inhibiting ROS-mediated tissue injury and tumor metastasis. Adv Drug Delivery Rev 61, 319-326. https://doi.org/10.1016/j.addr.2009.01.001
  19. Siquet C, Paiva F, Lima J, Reis S and Borges F (2006) Antioxidant profile of dihydroxy- and trihydroxyphenolic acids-; A structureactivity relationship study. Free Radical Res 40. 433-442. https://doi.org/10.1080/10715760500540442
  20. Smyth T., Ramachandran VN and Smyth WF. (2009) A study of the antimicrobial activity of selected naturally occurring and synthetic coumarins. Int J Antimicrob Agents 33, 421-426. https://doi.org/10.1016/j.ijantimicag.2008.10.022
  21. Soung MG, Lee YJ and Sung ND (2009) 3D-QSARs of herbicidal 2-N-phenyl- isoindolin-1-one analogues a new class of potent inhibitors of protox. Bull Kor Chem Soc 30, 613-617. https://doi.org/10.5012/bkcs.2009.30.3.613
  22. Tyagi YK, Kumar A, Raj HG, Vohra P, Gupta G, Kumari R, Kumar P and Gupta RK. (2005) Synthesis of novel amino and acetyl amino-4-methylcoumarins and evaluation of their antioxidant activity. Eur J Med Chem 40, 413-420. https://doi.org/10.1016/j.ejmech.2004.09.002
  23. Wold S, Johansson E and Cocchi M (1993) PLS-Partial least squares projections to latent structures, In 3D-QSAR in Drug Design: Theory, Methods and Applications. Kubinyi H (ed), ESCOM, Leiden, 523-550.
  24. Wu CR, Huang MY, Lin YT, Ju HY and Ching H (2007) Antioxidant properties of Cortex Fraxini and its simple coumarins. Food Chem 104, 1464-1471. https://doi.org/10.1016/j.foodchem.2007.02.023