Furopyridine Derivatives as Potent Inhibitors of the Wild Type, L858R/T790M, and L858R/T790M/C797S EGFR.

The treatment of patients with nonsmall cell lung cancer (NSCLC) using epidermal growth factor receptor (EGFR) inhibitors is complicated by drug-sensitive activating L858R/T790M and L858R/T790M/C797S mutations. To overcome drug resistance, a series of furopyridine (PD) compounds were virtually screened to identify potent EGFR inhibitors using molecular docking and molecular dynamics (MD) simulations based on the solvated interaction energy (SIE) method. Several PD compounds identified from virtual screening demonstrated the potential to suppress both wild-type and mutant forms of EGFR, with IC values in the nanomolar range.

Evaluation of chelating agents based on pyridine-azacrown compounds HPATA, PATAM, and HPATPA for Ga and Lu.

In this article, we present the synthesis and characterization of three macrocyclic chelators, HPATA, PATAM, and HPATPA, based on a pyridine-azacrown compound. Their complexation with Ga and Lu has been thoroughly investigated using MALDI TOF MS, H NMR spectroscopy, radiolabeling studies, and experiments in vitro with fetal bovine serum and a 1000-fold molar excess of HEDTA. Our studies have shown that the chelators HPATA and HPATPA form complexes at room temperature with both radionuclides (RCY > 80 % and > 90 % for complexes with HPATA and HPATPA after 30 min, respectively).

Double-Armed 18- and 21-Membered Macrocycles as Potential Chelators for Lead and Bismuth Radiopharmaceuticals.

With increasing clinical applications and interest in targeted alpha therapy, there is growing interest in developing alternative chelating agents for [Pb]Pb and [Bi]Bi that exhibit rapid radiolabeling kinetics and kinetic inertness. Herein we report the synthesis and detailed investigation of diacetate and dipicolinate 18- and 21-membered macrocyclic chelators BADA-18, BADA-21, BADPA-18, and BADPA-21 for the complexation of Pb and Bi ions with potential use in the preparation of radiopharmaceuticals. The formation of mononuclear complexes was established by using ESI-mass spectrometry, and their stability constants were determined by potentiometric titration.

Assessing the biocompatibility and stability of CeO nanoparticle conjugates with azacrowns for use as radiopharmaceuticals.

The application of nanoparticles is promising for the purposes of nuclear medicine due to the possibilities of using them as vectors and transporters of radionuclides. In this study, we have successfully synthesised conjugates of CeO nanoparticles and azacrown ligands. Then, the radiolabelling conditions with radionuclides Zn, Sc and Bi were selected and the kinetic stability of the complexes in biologically significant media was evaluated.

Phthalazine Sulfonamide Derivatives as Carbonic Anhydrase Inhibitors. Synthesis, Biological and in silico Evaluation.

Carbonic Anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide involved in several biological processes. They show a wide diversity in tissue distribution and their subcellular localization. Twenty-two novel phthalazine derivatives were designed, synthesized, and evaluated against four human isoforms: hCA I, hCA II, hCA IX, and hCA XII.