New Azacycles by One-Pot Three-Component Hantzsch-Like Synthesis of Tetra(hexa)azacyclopenta[a]anthracenes, Tetraazaindeno[5,4-b]fluorenes, and Oxatetraazacyclopenta[m]tetraphenes

Multicomponent reactions (MCRs) are envisaged as an entry point for the synthesis of heterocyclic compounds with interesting biological activities. An efficient approach to annelated tetra(hexa)azacyclopenta[a]anthracenes, tetraazaindeno[5,4-b]fluorenes, and oxatetraazacyclopenta[m]tetraphene was accomplished using a three-component reaction involving 7-amino-2-methyl-3-phenylpyrazolo[1,5-a]pyrimidin-5-one with aromatic aldehydes and the corresponding active 1,3-dicarbonyl compounds (namely, dimedone, 1,3-dimethylbarbituric acid, 1,3-indanedione, and 4-hydroxycoumarine). The reactions were conducted in glacial acetic acid at reflux for 5 h to give the desired products in good yields (62–83 %). The chemical constitutions of all new products were confirmed spectroscopically

Effect of Simulated Drought and Rainfall Fluctuation on Seedling Growth of Two Savannah Trees Species in Sudan: An Experimental Exploration = Szimulált aszály és csapadék ingadozás hatása két szavannai fafaj csemetéinek növekedésére Szudánban: egy kísérleti felfedezés

Climate change scenarios project that several regions, especially in dryland areas of sub-Saharan Africa, will undergo increasing aridity and, subsequently, expanding land degradation. The study aims to investigate the effect of two drying treatments on establishing and growing Hashab (Acacia senegal) and Boabab (Adansonia digitata) in nursery conditions. Through a 2×2 factorial experiment, seedlings grown in a mixture of silt and sand soil (2:3) were treated by irrigation intervals of one or two liters every three days for 14 weeks to simulate rainfall fluctuation patterns. Seedling germination rate, leaf number, stem height, and diameter were measured weekly; taproot length, shoot, and root dry weights were also assessed. The results showed that neither drying treatment significantly affected A. senegal and A. digitata seedling growth parameters. However, an interaction effect was found in the height and diameter for A. senegal and shoot dry weight for A. digitata. The study concluded that A. senegal and A. digitata seem tolerant to drying treatment. Therefore, the two species are recommended for afforestation programs in areas with relatively harsher conditions. Also, exposing the seedlings of these studied species to similar, extended periods of simulated drought (e.g., 6 – 12 months) is recommended for future studies. Az éghajlatváltozási forgatókönyvek szerint több régió, különösen a száraz területek a szubszaharai Afrikában, egyre szárazabbá válnak és ennek következtében a talajdegradáció is terjedni fog. A tanulmány célja a Hashab (Acacia senegal) és a Boabab (Adansonia digitata) két szárítási kezelésnek a csemetekerti körülmények közötti kialakulására és növekedésére gyakorolt hatásának vizsgálata. Egy 2×2 faktoriális kísérleten keresztül, amelyben magoncokat neveltünk homokos és iszapos talajkeverékben (2:3) öntözési intervallumokkal, amelyek 1 vagy 2 literes vízmennyiségeket kaptak minden 3. napon 14 hétig, hogy szimuláljuk a csapadékingadozásokat. A magoncok csírázási aránya, a levél- és a szár magassága, valamint átmérőjük hetente mérve lett, majd a hosszú gyökér, a hajtás és a gyökér száraz tömegeit értékeltük ki. Az eredmények azt mutatják, hogy egyik szárítási kezelés sem volt hatással az A. senegal és az A. digitata magoncok növekedési paramétereire. Azonban interakciós hatást találtunk az A. senegal magasságára és átmérőjére, valamint az A. digitata hajtás száraz tömegére. A tanulmány arra a következtetésre jutott, hogy mind az A. senegal, mind az A. digitata toleránsnak tűnik a szárítási kezeléssel szemben, ezért mindkét faj ajánlható az erdősítési programokhoz olyan területeken, ahol viszonylag szélsőségesebbek a körülmények. A jövőbeni vizsgálatok során érdemes volna a vizsgált fajok csemetéit hosszabb ideig (pl. 6-12 hónap) szimulált aszálynak kitenni

Unlocking the potential of approved drugs for the allosteric inhibition of tropomyosin-receptor kinase A using molecular docking and molecular dynamics studies

Tropomyosin-receptor kinase A (TrkA) is the primary isoform among the tropomyosin-receptor kinases that have been associated with human cancer development, contributing to approximately 7.4% of all cancer cases. TrkA represents an attractive target for cancer treatment; however, currently available TrkA inhibitors face limitations in terms of resistance development and potential toxicity. Hence, the objective of this study was to identify new allosteric-approved inhibitors of TrkA that can overcome these challenges and be employed in cancer therapy. To achieve this goal, a screening of 9,923 drugs from the ChEMBL database was conducted to assess their repurposing potential using molecular docking. The top 49 drug candidates, exhibiting the highest docking scores (−11.569 to −7.962 kcal/mol), underwent MM-GBSA calculations to evaluate their binding energies. Delanzomib and tibalosin, the top two drugs with docking scores of −10.643 and −10.184 kcal/mol, respectively, along with MM-GBSA dG bind values of −67.96 and −50.54 kcal/mol, were subjected to 200 ns molecular dynamic simulations, confirming their stable interactions with TrkA. Based on these findings, we recommend further experimental evaluation of delanzomib and tibalosin to determine their potential as allosteric inhibitors of TrkA. These drugs have the potential to provide more effective and less toxic therapeutic alternatives. The approach employed in this study, which involves repurposing drugs through molecular docking and molecular dynamics, serves as a valuable tool for identifying novel drug candidates with distinct therapeutic uses. This methodology can contribute to reducing the attrition rate and expediting the process of drug discovery