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

Efficient synthesis of novel bis(dihydropyrano[2,3c]pyrazoles), bis(4H-chromenes) and bis(dihydropyrano[3,2-c]chromenes) with amide functionality

A synthesis of novel bis(1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles), bis(4H-chromene-3-carbonitriles) and bis(dihydropyrano[3,2-c]chromenes), which are linked to aliphatic spacers via amide linkages was achieved via multicomponent reactions (MCR) of the appropriate bis-aldehyde with two equivalents of both of malononitrile and 3-methylpyrazol-5-one, dimedone or 4-hydroxycoumarin in a basic solution

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

Physiological Performance of Rabbits Administered Buffalo Milk Yogurts Enriched with Whey Protein Concentrate, Calcium Caseinate or Spirulina platensis

The present study examines the impacts of supplementing yogurt with 1% whey protein concentrate (WPC), Ca-caseinate (Ca-CN) and Spirulina platensis on the physiological performance of V-line rabbits receiving diets containing yogurt (at a dose of 5 g/kg body weight/day) and the different meat quality aspects. The results show that fat content was highest (p < 0.05) in yogurt fortified with Spirulina powder, but protein (%) was highest in yogurt enriched with WPC. Yogurt containing Spirulina powder showed a significant (p < 0.05) increase in total antioxidant activity. The final live body weight for G1 was higher than the other groups. However, additives affected the saddle, hind legs, liver and neck percentages significantly (p < 0.05). There were not significant differences for all groups in the forelegs, lung and heart percentages. LDL-cholesterol, total protein, globulin, albumin, creatinine and immunoglobulin M values were lowest (p < 0.05) in the WPC group. Significant improvements appeared in the small intestinal wall, microbiology, growth performance, serum biochemistry, organ histology and meat quality of the group receiving enriched yogurt. Yogurts enriched with WPC, Ca-CN and Spirulina platensis can be used as functional foods

Identification of Novel Natural Dual HDAC and Hsp90 Inhibitors for Metastatic TNBC Using e-Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Studies

Breast cancer (BC) is one of the main types of cancer that endangers women’s lives. The characteristics of triple-negative breast cancer (TNBC) include a high rate of recurrence and the capacity for metastasis; therefore, new therapies are urgently needed to combat TNBC. Dual targeting HDAC6 and Hsp90 has shown good synergistic effects in treating metastatic TNBC. The goal of this study was to find potential HDAC6 and Hsp90 dual inhibitors. Therefore, several in silico approaches have been used. An e-pharmacophore model generation based on the HDAC6-ligand complex and subsequently a pharmacophore-based virtual screening on 270,450 natural compounds from the ZINC were performed, which resulted in 12,663 compounds that corresponded to the obtained pharmacophoric hypothesis. These compounds were docked into HDAC6 and Hsp90. This resulted in the identification of three compounds with good docking scores and favorable free binding energy against the two targets. The top three compounds, namely ZINC000096116556, ZINC000020761262, and ZINC000217668954, were further subjected to ADME prediction and molecular dynamic simulations, which showed promising results in terms of pharmacokinetic properties and stability. As a result, these three compounds can be considered potential HDAC6 and Hsp90 dual inhibitors and are recommended for experimental evaluation