22917-75-5

Upstream product

• 25878-29-9 cis,syn-3,3'-dimethyl-1,1'-trimethylenebis(thymine) cyclobutadipyrimidine 
• 65-71-4 thymin 
• 22919-50-2 1-(3-bromopropyl)-5-methylpyrimidine-2,4(1H,3H)-dione 
• 109-64-8 1,3-dibromo-propane 
• 7288-28-0 2,4-bis(trimethylsiloxy)-5-methylpyrimidine 

Relevant academic research and scientific papers

NMR and UV Study of 1,1′-(α,ω-Alkanediyl)bis[thymine] and l,1′-(α,ω-Alkanediyl)bis[uracil]

Treatment of thymine or uracil with Br(CH2)nBr (n = 3-10) in the presence of t-BuOK gave 1,1′-(α,ω-alkanediyl)bis[thymine] or 1,1′-(α,ω-alkanediyl)bis[uracil] together with l-(ω-bromoalkyl)thymine or l-(ω-bromoalkyl)uracil. The structures of these products were determined on the basis of the coupling constants between 5- and 3-positions of uracil ring on the 1H NMR spectra. Molecular aggregation of the thymine and uracil rings of these compounds in aqueous solution was studied on the basis of their 1H NMR and UV spectra. A stacking interaction of the two thymine rings linked by shorter polymethylene chains such as trimethylene and tetramenthylene groups was observed.

Photoprotection of DNA (in vitro) by acyclothymidine dinucleosides

Excessive exposure to sunlight is primarily implicated in ultraviolet (UV) induced skin cancers worldwide. Direct absorption of UV radiation by DNA leads to the formation of cyclobutane pyrimidine dimers (CPDs) resulting in DNA damage. The molecular mechanisms involved in the mutagenicity of CPDs are well established. Photoprotection of the skin from the detrimental effects of UV is essential in preventing skin damage. A variety of formulations, which essentially contain UV filters have been used as photoprotective agents of the skin. These comprise aromatic and inorganic molecules, whose mechanism of action involves either absorption, reflection, or scattering of UV radiation. However, the downstream photoproducts of some of these molecules have undesirable characteristics which compromise their utility. A biomimetic approach involving structural analogs of nucleic acids can help overcome these limitations. Herein, we show the photoprotective action of acyclothymidine dinucleosides on both plasmid and cellular DNA.

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity

We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as evaluated by molecular docking analysis. The antimelanoma activity of novel photo-adducts was retained after loading into UV photo-protective lignin nanoparticles as stabilizing agent and efficient drug delivery system. Overall, these results support a combined antimelanoma and UV sunscreen strategy involving the use of photo-protective lignin nanoparticles for the controlled release of thymine dimers on the skin followed by their sacrificial transformation into photo-adducts and successive inhibition of melanoma and alert of cellular UV machinery repair pathways.

Triplet Energy Transfer versus Excited State Cyclization as the Controlling Step in Photosensitized Bipyrimidine Dimerization

Polymethylene-linked bipyrimidine models have been designed with different C5 substitutions and bridge lengths. Selective irradiation of 2′-methoxyacetophenone (2M) with the bipyrimidine models affords cyclobutane pyrimidine dimers, even in the presence of bulky substituents. Substitution at C5 affects both the relative triplet energies (ET(rel)) of the pyrimidines (Pyr) and the steric hindrance toward intermolecular energy transfer and intramolecular triplet Pyr? quenching. Photophysical studies showed that alkyl substitution resulted in a significant decrease in the ET(rel) value. Quenching of the triplet excited state of 2M by the Pyr derivatives was proven and established their quenching rate constants (kq). As a general trend, the thymine-containing compounds showed kq values higher than 109 M-1 s-1, while in the uracil and tert-butyluracil analogues, kq was markedly lower. These data are explained considering three different scenarios: (a) triplet energy transfer is the rate controlling step, (b) excited state cyclization is the rate controlling step, and (c) the rate controlling step switches along the reaction. Thus, by introducing variations in the substitution at C5, the length of the linking bridge, or the substrate concentration, it is possible to switch from a process governed by the intrinsic dimerization step to an energy transfer-controlled process.

SUNLESS TANNING COMPOUNDS AND COMPOSITIONS

The invention provides sunless tanning compositions comprising a compounds of formula (I): or a salt thereof as described herein as well as methods for tanning mammalian skin by contacting the skin with the compounds of formula (I) or compositions comprising compounds of formula (I).

AGENTS THAT PREVENT OR REPAIR SKIN DAMAGE

The invention provides compounds of formula I: or a salt thereof as described herein. The invention also provides dermatological compositions comprising a compound of formula I or mixtures of one or more compounds of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for protecting skin or DNA from photodamage or repairing photodamaged skin or DNA.

A Possible Chain Reaction in Photosensitized Splitting of Pyrimidine Dimers by a Protonated, Oxidized Flavin

Pyrimidine dimer cycloreversion was photosensitized by protonated 2',3',4',5'-tetraacetylriboflavin (ac4rfH+), whereas the protonated flavin radical (ac4rfH2.+) failed to sensitize detectable dimer splitting.In acetonitrile containing 0.075percent perchloric acid, the ac4rf absorption bands at 375 nm and 445 nm are replaced by a new band at 390 nm due to ac4rfH+.Irradiation of ac4rfH+ in the presence of cis,syn- or trans,syn-1,3-dimethyluracil dimer resulted in efficient cycloreversion to 1,3-dimethyluracil, probably induced by electron abstraction from the dimer by ac4rfH+ to produce the dimer radical cation.The quantum yields of splitting were large (Φspl = 0.35 and 1.5 for cis,syn and trans,syn isomers, respectively, at = 1.2 mM).Splitting quantum yields increased with dimer concentration in a quadratic fashion.These results are consistent with the occurance of a chain reaction propagated by monomer.+ + dimer -> monomer + dimer.+ in the case of the dimethyluracil dimers.The fluorescence of the protonated flavin (λem = 507 nm) was found to be quenched by the dimers.In the presence of small amounts of added water, however, both the fluorescence quenching and splitting were abolished.Two cis,syn dimers in which the N(1)- and N(1')-atoms were tethered via a trimethylene bridge exhibited quantum yields of approximately 0.02 at the above dimer concentration.A compound in which ac4rf is covalently bound to a pyrimidine dimer was also found to undergo splitting in acidified acetonitrile (Φ = 0.03).These values are more than 1 order of magnitude greater than those reported for unprotonated flavins.

Intramolecular Cyclization of 1-(3-Bromopropyl)uracils

The intramolecular O-alkylation of 1-(3-bromopropyl)uracils proceeds smoothly in basic conditions and yields cyclic ethers as the major products.This reaction competes with the intermolecular N-alkylation of uracil and its derivatives.The mechanism of this reaction is also discussed in terms of reactivity indices calculated using the HMO method.