Design and Synthesis of Topoisomerases-Histone Deacetylase Dual Targeted Quinoline-Bridged Hydroxamates as Anticancer Agents.

The multifactorial nature of cancer requires treatment that involves simultaneous targeting of associated overexpressed proteins and cell signaling pathways, possibly leading to synergistic effects. Herein, we present a systematic study that involves the simultaneous inhibition of human topoisomerases (hTopos) and histone deacetylases (HDACs) by multitargeted quinoline-bridged hydroxamic acid derivatives. These compounds were rationally designed considering pharmacophoric features and catalytic sites of the cross-talk proteins, synthesized, and assessed for their anticancer potential.

Primary squamous cell carcinoma of thyroid gland-First case report from state Punjab, India.

Primary squamous cell carcinoma of the thyroid is a very rare thyroid malignancy. In addition, due to its presentation as a locally advanced disease with a high tendency to metastasize, it has a poor prognosis and outcome. We report a 60-year-old male patient with PSCC, which was confirmed by immunohistochemistry on biopsy.

Quantification and severity grading of femoral vessel compression by adverse reactions to metal debris in metal-on-metal total hip arthroplasty.

Introduction: Metal-on-metal (MoM) total hip arthroplasty (THA) may cause adverse reactions to metal debris (ARMD). ARMD causing femoral vessel compression with serious complications has been described in case reports, but the rate of compression by ARMD is not known. This study aims to investigate the rate, and quantify the severity, of femoral vessel compression in MoM hips with ARMD lesions.

Targeting the Epidermal Growth Factor Receptor with Molecular Degraders: State-of-the-Art and Future Opportunities.

Epidermal growth factor receptor (EGFR) is an oncogenic drug target and plays a critical role in several cellular functions including cancer cell growth, survival, proliferation, differentiation, and motility. Several small-molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) have been approved for targeting intracellular and extracellular domains of EGFR, respectively. However, cancer heterogeneity, mutations in the catalytic domain of EGFR, and persistent drug resistance limited their use.

Improving Drug Delivery While Tailoring Prodrug Activation to Modulate and by Optimization of (Carbonyl)oxyalkyl Linker-Based Prodrugs of Atazanavir.

Structure-property relationships associated with a series of (carbonyl)oxyalkyl amino acid ester prodrugs of the marketed HIV-1 protease inhibitor atazanavir (), designed to enhance the systemic drug delivery, were examined. Compared to previously reported prodrugs, optimized candidates delivered significantly enhanced plasma exposure and trough concentration ( at 24 h) of in rats while revealing differentiated PK paradigms based on the kinetics of prodrug activation and drug release. Prodrugs incorporating primary amine-containing amino acid promoieties offered the benefit of rapid bioactivation that translated into low circulating levels of the prodrug while delivering a high value of .