Efficacy and safety of Kanglaite injection combined with chemotherapy for women breast cancer: A protocol for systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Breast cancer was the second cause of cancer death and approximately accounted for 30% of all newly diagnosed cancer in American women. Adjuvant chemotherapy is the preferred treatment approach for breast patients. Kanglaite injection (KI) was commonly used as adjuvant chemotherapy combined with chemotherapy for women breast cancer which could increase chemotherapy efficacy and alleviate chemotherapy drugs induced adverse events, however, the efficacy and safety for KI combined western medicine remains controversial. Thus, we conducted this protocol of systematic review and meta-analysis to estimate the efficacy and safety of KI combined with western medicine for women breast cancer. METHODS: This study will search electronic database included English medicals databases and Chinese databased up to May 2021. The main outcomes of this study include clinical efficacy rate. Adverse reaction rate, Karnofsky Performance Status and immune function were defined as the secondary outcomes. RESULTS: This protocol study will comprehensively evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer. CONCLUSION: This protocol for systematic review and meta-analysis will evaluate the efficacy and safety of KI combined with chemotherapy for women breast cancer, aiming to provide optimal therapy for women breast cancer patients.

Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections.

Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271.

Discovery of novel purine nucleoside derivatives as phosphodiesterase 2 (PDE2) inhibitors: Structure-based virtual screening, optimization and biological evaluation.

Phosphodiesterase 2 (PDE2) has received much attention for the potential treatment of the central nervous system (CNS) disorders and pulmonary hypertension. Herein, we identified that clofarabine (4), an FDA-approved drug, displayed potential PDE2 inhibitory activity (IC50 = 3.12 ±â€¯0.67 µM) by structure-based virtual screening and bioassay. Considering the potential therapeutic benefit of PDE2, a series of purine nucleoside derivatives based on the structure and binding mode of 4 were designed, synthesized and evaluated, which led to the discovery of the best compound 14e with a significant improvement of inhibitory potency (IC50 = 0.32 ±â€¯0.04 µM). Further molecular docking and molecular dynamic (MD) simulations studies revealed that 5'-benzyl group of 14e could interact with the unique hydrophobic pocket of PDE2 by forming extra van der Waals interactions with hydrophobic residues such as Leu770, Thr768, Thr805 and Leu809, which might contribute to its enhancement of PDE2 inhibition. These potential compounds reported in this article and the valuable structure-activity relationships (SARs) might bring significant instruction for further development of potent PDE2 inhibitors.

Novel Vilazodone-Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation.

Depression is one of the most frequent psychiatric complications of Alzheimer's disease (AD), affecting up to 50% of the patients. A novel series of hybrid molecules were designed and synthesized by combining the pharmacophoric features of vilazodone and tacrine as potential multitarget-directed ligands for the treatment of AD with depression. In vitro biological assays were conducted to evaluate the compounds; among the 30 hybrids, compound 1e showed relatively balanced profiles between acetylcholinesterase inhibition (IC50 = 3.319 ± 0.708 µM), 5-HT1A agonist (EC50 = 107 ± 37 nM), and 5-HT reuptake inhibition (IC50 = 76.3 ± 33 nM). Compound 1e displayed tolerable hepatotoxicity and moderate hERG inhibition activity, and could penetrate the blood-brain barrier in vivo. Furthermore, an oral intake of 30 mg/kg 1e·HCl could significantly improve the cognitive function of scopolamine-induced amnesia mice and alleviate the depressive symptom in tail suspension test. The effectivity of 1e validates the rationality of our design strategy.