For several years, cancer has increased in the population, being one of the main causes of death worldwide. This clinical pathology is associated with the activation/release of various biomolecules, including the Janus kinase family (JAKs). It is important to mention that some studies indicate that some JAK inhibitors (ruxolitinib and tofacitinib) may have a significant effect on some autoimmune diseases and cancer; however, some of these drugs can produce secondary effects such as herpes zoster, infectious, acute respiratory distress and others. The aim of this study was to evaluate the interaction of coumarin and its derivatives (compounds 2 to 24) with the JAK-3 surface. In this way, the Interaction of coumarin and their derivatives with JAK-3 was determined using the 3pjc protein and either decernotinib or tofacitinib drugs as theoretical tools on DockinServer program. The results showed differences in the aminoacid residues involved in the interaction of coumarin and their derivatives with 3pjc protein surface compared with decernotinib and tofacitinib. Besides, the inhibition constant (Ki) for coumarin derivatives 7, 9 and 10 was lower compared with tofacitinib. However, Ki was lower for 2, 5, 7, 8, 9, 10, and 24 compared with decernotinib. In conclusion, the coumarin derivatives 2, 5, 7, 8, 9, 10, and 24 could be good alternatives as JAK-3 inhibitors to decrease cancer cells growth.

Several oxazine derivatives have been synthesized; nevertheless, expensive reagents and special conditions are required. Therefore, in this study, two oxazine derivatives (2-chloro-3-{{2-[-(3-chloro-2-oxo-cyclobutyl)-(2,3-dimethoxy-9,10-dihydrostrychnid-10-yl)-amino]-ethyl}-[1,5-dimethyl-4-(1H-naphtho[1,2-e][1,3-oxazin-2-yl)-2-phenyl-2,3-dihydro-1H-pyrazol-3-yl]-amino}-cyclobutanone and 2-chloro-3-{{2-[(3-chloro-2-oxo-cyclobutyl)-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amino]-ethyl}-[1,5-dimethyl-4-(1H-naphtho[1,2-e][1,3]oxazin-2-yl)-2-phenyl-2,3-dihydro-1H-pyrazol-3-yl]-amino}-cyclobutanone) were synthesized using several strategies. The structure of compounds obtained was confirmed by elemental analysis, spectroscopy, and spectrometry data. In conclusion, the methods used offer some advantages such as good yields, simple procedure, low cost, and ease of workup.

B u çalışmanın amacı, inotropik aktivitelerini in vitro olarak değerlendirmek için iki adet 7,8-dioksabisiklo [4.1.1] oktan-3-il)-steroid türevini (bileşik 3 veya 4) sentezlemekti. İlk aşama, bazı kimyasal stratejiler kullanılarak iki 7,8-dioksabisiklo [4.1.1] oktan-3-il)-steroid türevinin hazırlanmasıyla başarıldı. Daha sonra, her iki steroid türevinin sol ventrikül basıncına (LVP) karşı inotropik aktivitesi, kontrol olarak Bay-k-8644, nifedipin, aucubin ve L-NAME kullanılarak izole edilmiş bir sıçan kalp modelinde değerlendirildi. Sonuçlar, bileşik 3'ün LVP'yi doza bağlı bir şekilde arttırdığını ve bu etkinin nifedipin tarafından inhibe edildiğini gösterdi. Diğer sonuçlar, bileşik 4'ün LVP'yi doza bağlı bir şekilde azalttığını ve bu etkinin L-NAME varlığında bloke edildiğini gösterdi. Tüm bu veriler, 1) Bileşik 3 tarafından uygulanan pozitif inotropik aktivitenin, L tipi kalsiyum kanalı aktivasyonu yoluyla olduğunu; 2) 4'ün negatif inotropik etkisi, nitrik oksit sentaz aktivasyonu ile olmuştur. Bu fenomen, bileşik 3 ve 4'ün kimyasal yapısına dahil olan farklı fonksiyonel gruplar nedeniyle olabilir.