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As angiogenesis plays a pivotal role in tumor progression and metastasis, leading to more cancer-related deaths, the angiogenic process can be considered as a target for diagnostic and therapeutic applications. The vascular endothelial growth factor receptor-1 (VEGR-1) and VEGFR-2 have high expression on breast cancer cells and contribute to angiogenesis and tumor development. Thus, early diagnosis through VEGFR-1/2 detection is an excellent strategy that can significantly increase a patient's chance of survival. In this study, the VEGFR1/2-targeting peptide VGB3 was conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), using 6-aminohexanoic acid (Ahx) as a spacer to prevent steric hindrance in binding. DOTA-Ahx-VGB3 was radiolabeled with Gallium-68 (68Ga) efficiently. An in vitro cell binding assay was assessed in the 4T1 cell line. The tumor-targeting potential of [68Ga]Ga-DOTA-Ahx-VGB3 was conducted for 4T1 tumor-bearing mice. Consequently, high radiochemical purity [68Ga]Ga-DOTA-Ahx-VGB3 (RCP = 98%) was prepared and stabilized in different buffer systems. Approximately 17% of the radiopeptide was internalized after 2 h incubation and receptor binding as characterized by the IC50 value being about 867 nM. The biodistribution and PET/CT studies revealed that [68Ga]Ga-DOTA-Ahx-VGB3 reached the tumor site and was excreted rapidly by the renal system. These features convey [68Ga]Ga-DOTA-Ahx-VGB3 as a suitable agent for the noninvasive visualization of VEGFR-1/2 expression. [ABSTRACT FROM AUTHOR]

The first example of intramolecular nucleophilic addition of 1,4-diazabutatriene to ester is disclosed. This approach provides a facile and versatile synthesis for functionalized 2H-1,4-benzoxazines under metal-, reagent-, and solvent-free conditions. Experimental and computational studies revealed the pivotal role of 1,5-acyl migration as the self-catalytic step in the reaction selectivity. [ABSTRACT FROM AUTHOR]

Cell invasion is an important process in cancer progression and recurrence. Invasion and implantation of cancer cells from their original place to other tissues, by disabling vital organs, challenges the treatment of cancer patients. Given the importance of the matter, many molecular treatments have been developed to inhibit cancer cell invasion. Because of their low production cost and ease of production, peptides are valuable therapeutic molecules for inhibiting cancer cell invasion. In recent years, advances in the field of computational biology have facilitated the design of anti‐cancer peptides. In our investigation, using computational biology approaches such as evolutionary analysis, residue scanning, protein–peptide interaction analysis, molecular dynamics, and free energy analysis, our team designed a peptide library with about 100 000 candidates based on A6 (acetyl‐KPSSPPEE‐amino) sequence which is an anti‐invasion peptide. During computational studies, two of the designed peptides that give the highest scores and showed the greatest sequence similarity to A6 were entered into the experimental analysis workflow for further analysis. In experimental analysis steps, the anti‐metastatic potency and other therapeutic effects of designed peptides were evaluated using MTT assay, RT‐qPCR, zymography analysis, and invasion assay. Our study disclosed that the IK1 (acetyl‐RPSFPPEE‐amino) peptide, like A6, has great potency to inhibit the invasion of cancer cells. [ABSTRACT FROM AUTHOR]

We present a novel green synthetic protocol for the construction of a broad range of substituted fused azabicyclo[3.3.1]nonadiquinoline scaffolds through a formic acid catalyzed formal [4 + 2] annulation/Mannich/dearomatization domino reaction. This unified strategy shows a broad substrate scope with high functional group tolerance, resulting in good to high yields under environmentally benign, transition-metal-free, low-cost, and operationally simple conditions. The current method outperforms existing methods in terms of green and sustainable conditions. The reaction mechanism was confirmed based on DFT calculations. [ABSTRACT FROM AUTHOR]