A Multitarget Approach toward the Development of 8‐Substituted Purines for Photoprotection and Prevention of UV‐Related Damage

Abstract

Ultraviolet (UV) light is the most abundant and significant modifiable risk factor for skin cancer and many other skin diseases such as early photo-aging. Across the solar radiation spectrum, UV light is the main cause behind skin problems. In the search for novel photoprotective compounds, a new series of 8-substituted purines were synthesized from commercially available 6-hydroxy-4,5-diaminopyrimidine hemisulfate or 4,5-diaminopyrimidine. All title compounds were investigated for their UV filtering, antioxidant, antifungal, and antiproliferative activities. For the photoprotection assays we used a diffuse transmittance technique to determine the sun protection factor (SPF) in vitro, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric ion reducing antioxidant power (FRAP) tests for evaluating the antioxidant activity of the more potent compounds. Among them, 8-(2,5-dihydroxyphenyl)-7H-purin-6-ol (compound 26) proved to be a good radical scavenger and is also endowed with broad-spectrum UVA filtering capabilities, suitable for further development as a protective molecule.

Skin Damages—Structure Activity Relationship of Benzimidazole Derivatives Bearing a 5-Membered Ring System

“…Besides, benzimidazole derivatives have a wide range of biological activities such as antibacterial, antimicrobial, antioxidant, anti-tuberculosis, antimalarial, antiulcer, antiallergic, antidiabetic as well as use in cardiovascular disease [ 19 , 20 , 21 , 22 ]. In addition to their therapeutic applications, benzimidazoles are known for their UV filtering ability [ 23 ]. Besides, 2-phenyl-5-(pyrrolidin-1-yl)-1-(3,4,5-trimethoxybenzyl)-1H-benzimidazole (PPTMB), 2-[4-(2-{4-[1-(2-Ethoxyethyl)-1H-benzimidazol-2-yl]-1-piperidinyl}ethyl)phenyl]-2-methylpropanoic acid (Bilastine) and 1-[(4-chlorophenyl)methyl]-2-methylbenzimidazole (Chlormidazole) are benzimidazole analogues, respectively used in the treatment of cancer, allergic rhino-conjunctivitis and fungal infection [ 24 ].…”

“…Besides, benzimidazole derivatives have a wide range of biological activities such as antibacterial, antimicrobial, antioxidant, anti-tuberculosis, antimalarial, antiulcer, antiallergic, antidiabetic as well as use in cardiovascular disease [19][20][21][22]. In addition to their therapeutic applications, benzimidazoles are known for their UV filtering ability [23]. Besides, 2-phenyl-5…”

System-oriented optimization of multi-target 2,6-diaminopurine derivatives: Easily accessible broad-spectrum antivirals active against flaviviruses, influenza virus and SARS-CoV-2

“…The induction of oxidative stress is in fact recognized as a common trigger of exacerbation in diseases caused by different viruses, including flavivirus, coronavirus and, particularly, Influenza virus [ 27 ]. A few literature reports show that opportune functionalization of the purine scaffold can lead to derivatives also endowed with antioxidant properties by scavenging reactive oxygen species (ROS) [ [28] , [29] , [30] ]. Among the many possible functionalization options, we were intrigued by a recent work from the Feringa group, describing the development of photoswitchable purine derivatives bearing an azobenzene moiety in C6 [ 31 ].…”