👤 Torki A Zughaibi

Alzheimer's disease (AD) poses a significant health challenge worldwide, affecting millions of individuals, and projected to increase further as the global population ages. Current pharmacological interventions primarily target acetylcholine deficiency and amyloid plaque formation, but offer limited efficacy and are often associated with adverse effects. Given the multifactorial nature of AD, there is a critical need for novel therapeutic approaches that simultaneously target multiple pathological pathways. Targeting key enzymes involved in AD pathophysiology, such as acetylcholinesterase, butyrylcholinesterase, beta-site APP cleaving enzyme 1 (BACE1), and gamma-secretase, is a potential strategy to mitigate disease progression. To this end, our research group has conducted comprehensive in silico screening to identify some lead compounds, including IQ6 (SSZ), capable of simultaneously inhibiting the enzymes mentioned above. Building upon this foundation, we synthesized SSZ, a novel multitargeted ligand/inhibitor to address various pathological mechanisms underlying AD. Chemically, SSZ exhibits pharmacological properties conducive to AD treatment, featuring pyrrolopyridine and N-cyclohexyl groups. Preclinical experimental evaluation of SSZ in AD rat model showed promising results, with notable improvements in behavioral and cognitive parameters. Specifically, SSZ treatment enhanced locomotor activity, ameliorated gait abnormalities, and improved cognitive function compared to untreated AD rats. Furthermore, brain morphological analysis demonstrated the neuroprotective effects of SSZ, attenuating Aβ-induced neuronal damage and preserving brain morphology. Combined treatment of SSZ and conventional drugs (DON and MEM) showed synergistic effects, suggesting a potential therapeutic strategy for AD management. Overall, our study highlights the efficacy of multitargeted ligands like SSZ in combating AD by addressing the complex etiology of the disease. Further research is needed to elucidate the full therapeutic potential of SSZ and the exploration of similar compounds in clinical settings, offering hope for an effective AD treatment in the future. Show less

Breast cancer (BC) is the most prevalent cancer in women and remains the leading cause of cancer-related mortality globally. Its development is influenced by multiple factors, including genetics, environmental, aging, and modulation of various signaling pathways. The heterogeneity of BC together with the emergence of treatment resistance and recurrence have prompted researchers to explore and develop new therapeutic approaches. Recently, oncology research has primarily focused on the development of targeted therapies against molecular abnormalities in BC. These therapies include monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates, PI3K/Akt/mTOR pathway inhibitors, CDK 4/6 inhibitors, PARP inhibitors, antiangiogenic agents, and various other targeted drugs. Immunomodulatory strategies, including immune checkpoint inhibitors (anti-PD-1/PD-L1), CTLA-4 blockers, adoptive T-cell therapy, and cancer vaccines, stimulate immune response against cancer cells. Epigenetic therapies like DNMT and HDAC inhibitors have also shown promise in BC treatment. This review highlights how innovative approaches like targeting intratumoral heterogeneity, liquid biopsy for resistance mutation detection, bypass mechanisms ( Show less