Drug Res (Stuttg) 2013; 63(12): 650-656
DOI: 10.1055/s-0033-1351287
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Non-cytotoxic Dimedone Derivatives: Structure, Antiradical and UV Protective Studies

P. V. Joshi
1   Centre for Materials Characterization, National Chemical Laboratory, Pune, India
K. S. Mundhe
2   Dr. T. R. Ingle Research Laboratory, Department of Chemistry, Sir Parashurambhau College, Pune, India
A. A. Khan
3   Institute of Bioinformatics & Biotechnology, University of Pune, Pune, India
R. L. Gawade
1   Centre for Materials Characterization, National Chemical Laboratory, Pune, India
N. R. Deshpande
2   Dr. T. R. Ingle Research Laboratory, Department of Chemistry, Sir Parashurambhau College, Pune, India
R. V. Kashalkar
2   Dr. T. R. Ingle Research Laboratory, Department of Chemistry, Sir Parashurambhau College, Pune, India
V. G. Puranik
1   Centre for Materials Characterization, National Chemical Laboratory, Pune, India
› Author Affiliations
Further Information

Publication History

received 15 May 2013

accepted 07 July 2013

Publication Date:
31 July 2013 (online)


Dimedone derivatives (L1–L4) with methyl substitution at the ortho, para and meta positions were synthesized and their anti-radical, photoreactive and photostability activities were evaluated. All compounds are characterized by spectroscopic techniques and by single crystal X ray diffraction. UV exposure experiments on pBR322 showed inhibition of plasmid DNA fragmentation by UV radiation in a dose dependent manner. Radical scavenging assays and ESR spectra indicate that these compounds possess antiradical activities and do not photodegrade to form other side products as confirmed by chromatographic analysis. They are non-cytotoxic towards human keratinocyte HaCaT cell line indicates their potentiality in sunscreens.

Supporting Information

  • References

  • 1 Schroeder P, Krutmann J. What is needed for a sunscreen to provide complete protection. Skin Therapy Lett 2010; 15: 4
  • 2 Cheo DL, Meira LB, Burns DK et al. Ultraviolet B radiation-induced skin cancer in mice defective in the Xpc, Trp53, and Apex (HAP1) genes: genotype-specific effects on cancer predisposition and pathology of tumors. Cancer Res 2000; 60: 1580
  • 3 Agar NS, Halliday GM, Barnetson R et al. The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: a role for UVA in human skin carcinogenesis. Proc Natl Acad Sci USA 2004; 1011: 4954
  • 4 Sinha RP, Hader DP. UV-induced DNA damage and repair: a review. Photochem Photobiol Sci 2002; 1: 225
  • 5 Lopez-Camarillo C, Ocampo EA, Casamichana ML et al. Protein Kinases and Transcription Factors Activation in Response to UV-Radiation of Skin: Implications for Carcinogenesis. Int J Mol Sci 2012; 13: 142
  • 6 Seite S, Colige A, Piquemal-Vivenot P et al. A full-UV spectrum absorbing daily use cream protects human skin against biological changes occurring in photoaging. Photodermatol Photoimmunol Photomed 2000; 16: 147
  • 7 Gasparro FP, Mitchnick M, Nash JF. A review of sunscreen safety and efficacy. Photochem Photobiol 1998; 68: 243
  • 8 Cockell CS, Knowland J. Ultraviolet radiation screening compounds. Biol Rev 1999; 74: 311
  • 9 Pallela R, Na-Young Y, Kim SK. Anti-photoaging and photoprotective compounds derived from marine organisms. Mar Drugs 2010; 8: 1189
  • 10 Lucarini M, Pedrielli P, Pedulli GF et al. Bond Dissociation Energies of the N−H Bond and Rate Constants for the Reaction with Alkyl, Alkoxyl, and Peroxyl Radicals of Phenothiazines and Related Compounds. J Am Chem Soc 1999; 121: 11546
  • 11 Newman MD, Stotland M, Ellis JI. The safety of nanosized particles in titanium dioxide- and zinc oxide-based sunscreens. J Am Acad Dermatol 2009; 61: 685
  • 12 Iavicoli I, Leso V, Fontana L et al. Toxicological effects of titanium dioxide nanoparticles: a review of in vitro mammalian studies. Eur Rev Med Pharmacol Sci 2001; 15: 481
  • 13 Lam HW, Cooke PA, Pattenden G et al. Journal of the Chemical Society-Perkin Transaction 1, Structure and total synthesis of benzylthiocrellidone, a novel dimedone-based vinyl sulfide from the sponge Crella spinulata. J Chem Soc Perkin Trans 1999; 8: 847
  • 14 Martinez R, Gustavo AJ, Ramirez MT et al. Tetrahydropyrrolo[3,2-c]azepin-4-ones as a new class of cytotoxic compounds. Bioorg Med Chem 2006; 14: 4007
  • 15 El-Sabbagh OI, Shabaan MA, Kadry HH et al. Synthesis of new nonclassical acridines, quinolines, and quinazolines derived from dimedone for biological evaluation. Arch Pharm (Weinheim) 2010; 343: 519
  • 16 Acton N, Brossi A, Newton DL et al. Potential prophylactic antitumor activity of retinylidene 1,3-diketones. J Med Chem 1980; 23: 805
  • 17 Dunford R, Salinaro A, Cai L et al. Chemical oxidation and DNA damage catalysed by inorganic sunscreen ingredients. FEBS Lett 1997; 418: 87
  • 18 Sheldrick GM. SHELX-97 Program for Crystal Structure Solution and Refinement. University of Gottingen; Germany: 1997
  • 19 Brand-Williams W, Cuvelier ME, Berset C. Use of free radical method to evaluate antioxidant activity. LWT-Food Sci Technol 1995; 28: 25
  • 20 Duan X, Wu G, Jiang Y. Evaluation of the antioxidant properties of litchi fruit phenolics in relation to pericarp browning prevention. Molecules 2007; 12: 759
  • 21 Tai A, Sawano T, Ito H. Antioxidative properties of vanillic acid esters in multiple antioxidant assays. Biosci Biotechnol Biochem 2012; 76: 314
  • 22 Metelitza DI, Eryomin AN, Sviridov DO et al. Initiation and inhibition of free radical processes in H2O2-metmyoglobin (methemoglobin)-2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) systems. Biochemistry (Mosc) 2001; 66: 505
  • 23 Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem 1996; 239: 70
  • 24 Calliste CA, Trouillas P, Allais DP et al. Free radical scavenging activities measured by electron spin resonance spectroscopy and B16 cell antiproliferative behaviors of seven plants. J Agric Food Chem 2001; 49: 3321
  • 25 Gonzalez H, Tarras-Wahlberg N, Strömdahl B et al. Photostability of commercial sunscreens upon sun exposure and irradiation by ultraviolet lamps. BMC Dermatol 2007; 7: 1
  • 26 Gaspar LR, Maia Campos PM. Evaluation of the photostability of different UV filter combinations in a sunscreen. Int J Pharm 2006; 307: 123
  • 27 Demas JN, Crosby GA. The measurement of photoluminescence quantum yields. J Phys Chem 1971; 75: 991
  • 28 Mosman T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983; 65: 55
  • 29 Bertolasi V, Gilli P, Ferretti V et al. Intermolecular N-H…O Hydrogen Bonding Assisted by Resonance. II. Self Assembly of Hydrogen-Bonded Secondary Enaminones in Supramolecular Catemers. Acta Cryst B 1998; 54: 50
  • 30 Nagaiah K, Purnima K, Sreenu D et al. Phosphomolybdic Acid (PMA) Catalyzed Highly Efficient and Rapid Synthesis of β-Enaminones. Synthetic Commun 2012; 42: 461
  • 31 Nguyen J, Ma Y, Luo T et al.. Direct observation of ultrafast-electron-transfer reactions unravels high effectiveness of reductive DNA damage. Proc Natl Acad Sci USA 2011; 108: 11778
  • 32 Tonnesen HH, Karlsen J, van Henegouwen GB. Studies on curcumin and curcuminoids. VIII. Photochemical stability of curcumin. Z Lebensm Unters Forsch 1986; 183: 116
  • 33 Bengmark S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr 2006; 30: 45
  • 34 Tsai KD, Lin JC, Yang SM et al. Curcumin Protects against UVB-Induced Skin Cancers in SKH-1 Hairless Mouse: Analysis of Early Molecular Markers in Carcinogenesis. Evid Based Complement Alternat Med 2012; 2012: 593952 11 pg
  • 35 Singh I, Calvo C. The Crystal Structure of Dimedone. Can J Chem 1975; 53: 1046
  • 36 Allenburg R, Kissel T. The Human Keratinocyte Cell Line HaCaT: An In Vitro Cell Culture Model for Keratinocyte Testosterone Metabolism. Pharma Res 1999; 16: 776
  • 37 Crystallographic data of L1–L4 has been deposited with the Cambridge Crystallographic Data Centre: CCDC 879227–879230 Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK