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Design, synthesis and evaluation of novel dualistic molecules provided with UV filtering and scavenging capabilities

Scalambra, Emanuela (2012) Design, synthesis and evaluation of novel dualistic molecules provided with UV filtering and scavenging capabilities. PhD Thesis , Università degli studi di Ferrara.

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    UV rays are the most dangerous radiation reaching the earth surface; the skin is within organs most affected, since it is directly exposed to sunlight and because of the presence of chromophores, such as melanin, DNA, RNA, proteins, lipids, trans-urocanic acid, and aromatic amino acids. Harmful effects of UV rays are not only due to direct damages, but also to indirect damages, caused by over-production of radical species. The skin has its own antioxidant defences, to deal with UV-induced oxidative stress; however, excessive and chronic exposure to UV radiation can overcome the cutaneous antioxidant capacity, leading to oxidative stress that may result in skin disorders, immunosuppression, premature skin aging and development of melanoma and non-melanoma skin cancers. Since detrimental effects of UV rays are due to direct absorption of UV radiation and to over-production of reactive oxygen species, it is important to provide a complete photoprotection by screening UV radiation and by scavenging reactive oxygen species. To this purpose, the aim of the present work was to develop new compounds provided with both UV filtering and antioxidant capabilities. From the screening of commercial available UV filters, 2-Phenyl-1Hbenzimidazole- 5-sulphonic acid (PBSA) was selected as ideal compound for our studies because of its lack of antioxidant activity. With the aim to achieve antioxidant capacity and maintaining the filtering activity, PBSA was modified introducing hydroxyls on the phenyl ring and also substituting the functional group in position 5 of the benzimidazolic ring to evaluate the influence of this moiety on filtering and antioxidant capabilities. To assess the antioxidant power of the molecules DPPH, PCL and FRAP assays were performed. Generally all the new designed molecules were endowed with better antioxidant capacities than lead compound; the most active were compounds 3, 8 and 12, which have two hydroxyl moieties on phenyl ring. In addiction to antioxidant activity, the introduction of auxochroms on the phenyl ring of PBSA have shifted UV spectrum absorption toward longer wavelengths, indeed new compounds show a better UVA/UVB ratio and higher critical wavelength values then PBSA. The products were tested to verify cytotoxicity and phototoxicity in human keratinocytes. Particularly interesting are compound 3, 8 and 12, which satisfy the requirements of high filtering and antioxidant activity and are devoid of cytotoxicity and phototoxicity. These three compounds were finally tested for stability and photostability in cosmetic formulation. Results of accelerated stability studies suggest that they are less stable than parent compound, this can be explained by the higher reactivity of molecules provided with important antioxidant power, however, stability of compound 12 did not differ very much from PBSA. In photostability studies products 8 seems the less photostable but its degradation rate still remains lower than 10%. The best results are achieved by compounds 3, which degrades only a little more than PBSA, and most of all with product 12 that shows higher photostability than lead compound with a degradation rate lower than 2%. The best candidates to become UV filter products provided with antioxidant activities are compound 3, 8 and 12, that are still under study to further investigate their properties.

    Item Type:Thesis (PhD Thesis)
    Date:28 March 2012
    Tutor:Manfredini, Stefano
    Coordinator:Manfredini, Stefano
    Institution:Università degli studi di Ferrara
    Divisions:Dipartimento > Scienze farmaceutiche
    Subjects:Area 03 - Scienze chimiche > CHIM/08 Chimica farmaceutica
    Uncontrolled Keywords:antioxidants, sunscreens, photostability
    Deposited on:13 Feb 2013 15:00


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