Some new Bis-pyrazoline hybrids 8–17 with dual EGFR and BRAF^V600E inhibitors have been developed. The target compounds were synthesized and tested in vitro against four cancer cell lines. Compounds 12, 15, and 17 demonstrated strong antiproliferative activity with GI₅₀ values of 1.05 µM, 1.50 µM, and 1.20 µM, respectively. Hybrids showed dual inhibition of EGFR and BRAF^V600E. Compounds 12, 15, and 17 inhibited EGFR-like erlotinib and exhibited promising anticancer activity. Compound 12 is the most potent inhibitor of cancer cell proliferation and BRAF^V600E. Compounds 12 and 17 induced apoptosis by increasing caspase 3, 8, and Bax levels, and resulted in the downregulation of the antiapoptotic Bcl2. The molecular docking studies verified that compounds 12, 15, and 17 have the potential to be dual EGFR/BRAF^V600E inhibitors. Additionally, in silico ADMET prediction revealed that most synthesized bis-pyrazoline hybrids have low toxicity and adverse effects. DFT studies for the two most active compounds, 12 and 15, were also carried out. The values of the HOMO and LUMO energies, as well as softness and hardness, were computationally investigated using the DFT method. These findings agreed well with those of the in vitro research and molecular docking study.

A series of novel 3-cyanopyridone/pyrazoline hybrids (21–30) exhibiting dual inhibition against EGFR and BRAF^V600E has been developed. The synthesized target compounds were tested in vitro against four cancer cell lines. Compounds 28 and 30 demonstrated remarkable antiproliferative activity, boasting GI₅₀ values of 27 nM and 25 nM, respectively. These hybrids exhibited dual inhibitory effects on both EGFR and BRAF^V600E pathways. Compounds 28 and 30, akin to Erlotinib, displayed promising anticancer potential. Compound 30 emerged as the most potent inhibitor against cancer cell proliferation and BRAF^V600E. Notably, both compounds 28 and 30 induced apoptosis by elevating levels of caspase-3 and -8 and Bax, while downregulating the antiapoptotic Bcl2 protein. Molecular docking studies confirmed the potential of compounds 28 and 30 to act as dual EGFR/BRAF^V600E inhibitors. Furthermore, in silico ADMET prediction indicated that most synthesized 3-cyanopyridone/pyrazoline hybrids exhibit low toxicity and minimal adverse effects.

The emergence of antibiotic-resistant Streptococcus pneumoniae necessitates the discovery of novel therapeutic agents. This study investigated the antimicrobial potential of green-synthesized gold nanoparticles (AuNPs) fabricated using Arthrospira platensis extract. Characterization using Fourier transform infrared spectroscopy revealed the presence of functional groups such as ketones, aldehydes, and carboxylic acids in the capping agents, suggesting their role in AuNP stabilization. Transmission electron microscopy demonstrated the formation of rod-shaped AuNPs with a mean diameter of 134.8 nm, as determined by dynamic light scattering, and a zeta potential of −27.2 mV, indicating good colloidal stability. The synthesized AuNPs exhibited potent antibacterial activity against S. pneumoniae, with a minimum inhibitory concentration (MIC) of 12 μg/mL, surpassing the efficacy of the control antibiotic, tigecycline. To elucidate the underlying mechanisms of action, an untargeted metabolomic analysis of the A. platensis extract was performed, identifying 26 potential bioactive compounds belonging to diverse chemical classes. In silico studies focused on molecular docking simulations revealed that compound 22 exhibited a strong binding affinity to S. pneumoniae topoisomerase IV, a critical enzyme for bacterial DNA replication. Molecular dynamics simulations further validated the stability of this protein–ligand complex. These findings collectively highlight the promising antimicrobial potential of A. platensis-derived AuNPs and their constituent compounds, warranting further investigation for the development of novel anti-pneumococcal therapeutics.

A novel series of hybrid compounds comprising quinazolin-4-one and 3-cyanopyridin-2-one structures has been developed, with dual inhibitory actions on both EGFR and BRAF^V600E. These hybrid compounds were tested in vitro against four different cancer cell lines. Compounds 8, 9, 18, and 19 inhibited cell proliferation significantly in the four cancer cells, with GI₅₀ values ranging from 1.20 to 1.80 µM when compared to Doxorubicin (GI₅₀ = 1.10 µM). Within this group of hybrids, compounds 18 and 19 exhibited substantial inhibition of EGFR and BRAF^V600E. Molecular docking investigations provided confirmation that compounds 18 and 19 possess the capability to inhibit EGFR and BRAF^V600E. Moreover, computational ADMET prediction indicated that most of the newly synthesized hybrids have low toxicity and minimal side effects.