Macrocyclic triamine disulfonamides can be synthesized by double Tsuji–Trost N-allylation reaction of open-chain disulfonamides with 2-alkylidene-1,3-propanediyl bis(carbonates). The previously used Atkins–Richman macrocyclization method generally gives lower yields and requires more tedious purification of the product. Solvent, palladium source, ligand, and concentration have all been varied to optimize the yields of two key 12-membered ring bioactive compounds, CADA and VGD020. The new approach tolerates a wide range of functional groups and gives highest yields for symmetrical compounds in which the acidities of the two sulfonamide groups are matched, although the yields of unsymmetrical compounds are still generally good. The method has also been extended to the synthesis of 11-membered rings, pyridine-fused macrocycles, and products bearing an ester or aryl substituent on the exocyclic double bond.
Among the several anthropogenic factors, power lines are increasingly regarded as one of the most significant hazards to bird species, primarily owing to collisions and electrocutions. Nepal has comparatively fewer studies on the impact of power line collisions and electrocution on birds compared with developed nations. From November 2021 to May 2022, we assessed the effect of power line collisions and electrocutions on the mortality of birds in the Putalibazar Municipality of the Syangja district of Nepal. We established 117 circular plots in diverse habitats, including agricultural lands, forests, settlements, and river basins, along a 30.6 km long distribution line. Within 18 plots, we detected 43 fatalities of 11 species (17 individuals of six species due to collision and 26 individuals of eight species due to electrocution). House Swift ( Apus nipalensis ) and Common Myna ( Acridotheres tristis ) were the primary victims of the collision, whereas House Crow ( Corvus splendens ) and Rock Pigeon ( Columba livia ) were frequently observed electrocuted. We also recorded the electrocution of the critically endangered White‐rumped Vulture ( Gyps bengalensis ). The total rate of bird power line collisions per kilometer was 0.55 birds, while the total electrocution rate per 10 poles was 2.22. The bird abundance, distance to agricultural regions, and proximity to human settlements were found to have a strong relationship with the mortality of birds caused by power lines. In order to reduce power line collisions and electrocution fatalities, we recommend conducting a detailed bird population study prior to determining the route of distribution lines.
The chemokine receptor CXCR4 acts as a key cell surface receptor in HIV infections, multiple forms of cancer, and various other pathologies, such as rheumatoid arthritis and asthma. Macrocyclic polyamines and their metal complexes are known to exert anti-HIV activity, many acting as HIV entry inhibitors by specifically binding to CXCR4. Three series of pyridopentaazacylopentadecanes, in which the pyridine ring is fused to zero, one, or two saturated six-membered rings, were synthesized by manganese(ii)-templated Schiff-base cyclization of triethylenetetramine with various dicarbonyl compounds. By evaluating these macrocyclic polyamines and their complexes with Mn(2+), Cu(2+), Fe(3+), and Zn(2+), we have discovered novel CXCR4-binding compounds. The MnCl2 complex of a new pentaazacyclopentadecane with one fused carbocyclic ring (11) was found to have the greatest potency as an antagonist of the chemokine receptor CXCR4 (IC50: 0.014 μM), as evidenced by inhibiting binding of CXCL12 to PBMCs (peripheral blood mononuclear cells). Consequently, this compound inhibits replication of the CXCR4-using (X4) HIV-1 strain NL4-3 in the TZM-bl cell line with an IC50 value of 0.52 μM and low cytotoxicity (CC50: >100 μM). In addition, 18 other compounds were evaluated for their interaction with CXCR4 via their ability to interfere with ligand chemokine binding and HIV entry and infection. Of these, the metal complexes of the two more hydrophobic series with one or two fused carbocyclic rings exhibited the greatest potency. The Zn(2+) complex 21 was among the most potent, showing that redox activity of the metal center is not associated with CXCR4 antagonist activity.
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