摘要：Gatifloxacin eye drops are frequently used in eye *** such formulations have a major drawback *** duration of action and usually require 4e6 times installations daily.A chitosan coated niosomal formulation of gatifloxain was purposed to show a longer retention time on eyes and subsequent reduction in dosing *** were prepared by solvent injection method using cholesterol and *** extensive optimization of formulation was done using different ratios of cholesterol,Span-60 and drug,revealed NS60-5(cholesterol:span-6050:50 and drug content of 20 mg)to be the optimized niosome ***60-5 had shown a highest entrapment efficiency of 64.9±0.66%with particle size 213.2±1.5 nm and zeta potential
34.7±2.2 *** niosomes were also coated with different concentrations of chitosan and *** studies had revealed that optimized niosomes(86.77±1.31%)had increased the transcorneal permeation of Gatifloxacin more than two fold than simple drug solution(37.19±1.1%).Longer retention potential of the coated niosomes was further verified by fluorescence *** revealed that simple dye solution got easily washed out with in 6 *** uncoated niosomes(NS60-5)showed a longer retention(more than 6 h),which was further enhanced in case of coated niosomes ***60-1(more than 12 h).Antimicrobial studies had shown the better efficacy of CNS60-1(zone of inhibition)when compared to marketed *** final chitosan formulation was found to have shown better ocular tolerability as demonstrated by corneal hydration test histopathology investigations.

摘要：A series of 2-（arylmethylidene）-2,3-dihydro-1-benzofuran-3-one derivatives（aurones, 1–20） were synthesized and screened for their inhibitory activity against h MAO. Seventeen compounds（1–5, 7–17,19） were found to be selective towards h MAO-B, while two were non-selective（6 and 20） and one（18）selective towards h MAO-A. Compound 17（Ki = 0.10 0.01 mmol/L） was found to be equally potent and selective towards h MAO-B, when compared with the standard drug Selegiline（Ki = 0.12 0.01 mmol/L）.Nature and position of substitution in aryl ring at 2nd position of benzofuranone influences h MAO-B inhibitory potency, while their structural bulkiness influences selectivity between h MAO-A and h *** docking simulation was also carried out to understand the interaction of inhibitor with the enzyme at molecular level, and we found the docking results were in good agreement with the experimental values. Comparison of the activity profile of the aurones with their corresponding flavones reported earlier by our group revealed that there exists no difference in potency as well as selectivity.

摘要：Polypharmacology,which focuses on designing drugs to target multiple receptors,has emerged as a new paradigm in drug *** rationally design multi-target drugs,it is fundamental to understand protein-ligand interactions on a proteome *** have developed a Proteome-wide Off-target Pipeline （POP） that integrates ligand binding site analysis,protein-ligand docking,the statistical analysis of docking scores,and electrostatic potential *** utility of POP is demonstrated by a case study,in which the molecular mechanism of anti-cancer effect of Nelfinavir is *** combining structural proteome-wide off-target identification and systems biology,it is possible for us to correlate drug perturbations with clinical outcomes.

摘要：Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents. Administration of these drugs with siRNA is an efficacious strategy in this battle. Here, the present study tried to incorporate siRNA and paclitaxel(PTX) simultaneously into a novel nanocarrier. The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA) and glucose(Glu) onto its surface. The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCopolyethyleneimine(FeCo-PEI) nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG) gene delivery system. Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA), FeCo-PEI-PLA-PEG-Glu(NPsB) and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB) nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay. Besides, siRNA-FAM internalization was investigated by fluorescence microscopy. The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations. Meanwhile, siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474 cell lines. NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/***, they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu. We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

摘要：The macrophage migration inhibitory factor has been implicated in a number ofimmune and inflammatory processes. MIF presents particular opportunities for drug design anddevelopment with potential therapeutic applications. Drug design strategies taking intoconsideration of specific stereochemical and tautomeric requirements in the interaction of MIF withsubstrates and inhibitors allow several novel structures to be designed. Our investigationssuccessfully explored the tautomeric and stereochemical aspects of new compounds of the2-phenylpyruvic acid type, both experimentally, through synthesis and structural investigations andcomputationally, through molecular mechanics and quantum mechanics calculations.

摘要：Over the past years, significant efforts have been devoted to explore novel drug delivery and detection strategies for simultaneous therapy and diagnostics. The development of biotinylated polyurethane-urea nanoparticles as theranostic nanocarriers for targeted drug and plasmid delivery, for fluorescence detection of human hepatocellular carcinoma cells, is described herein. These targeted nanoparticles are specifically designed to incorporate biotin into the polymeric matrix, since many tumor types overexpress receptors for biotin as a mechanism to boost uncontrolled cell growth. The obtained nanoparticles were spherical, exhibited an average diameter ranging 110-145 nm, and showed no cytotoxicity in healthy endothelial cells. Biotinylated nanoparticles are selectively incorporated into the perinuclear and nuclear area of the human hepatocellular carcinoma cell line, HepG2, in division, but not into growing, healthy, human endothelial cells. Indeed, the simultaneous incorporation of the anticancer drugs, phenoxodiol or sunitinib, together with plasmid DNA encoding green fluorescent protein, into these nanoparticles allows a targeted pharmacological antitumor effect and furthermore, selective transfection of a reporter gene, to detect these cancer cells. The combined targeted therapy and detection strategy described here could be exploited for liver cancer therapy and diagnostics, with a moderate safety profile, and may also be a potential tool for other types of cancer.

摘要：目的:评价一种中药植物鞭檐犁头尖(***)作为抗癌药物的临床前研究的系统综述。方法:对Scopus、PubMed、Web of Science、ScienceDirect、LILACS、EBSCO Medline、Mendeley等7个数据库进行全面检索,检索时间截止到2023年9月8日。排除了临床试验和非原创的同行评议报告后,鞭檐犁头尖的提取物,组成,或分离化合物的体内外研究且经过同行评审的英文文献均被纳入。本研究定性评估了鞭檐犁头尖对不同肿瘤细胞、肿瘤大小和作用机制的有效性。证据质量由三名独立评估人员使用ToxRTool进行评估,并验证其一致性。结果:检索后共纳入27项研究:22项体外研究,4项体内研究,1项体内外研究。结果发现鞭檐犁头尖对白血病、乳腺癌、结直肠癌和肺癌有效。大多数研究的评估为“有限制的可靠”。鞭檐犁头尖通过阻断细胞周期、活化caspase-3/-9、分解PARP、裂解DNA、减少生存素含量、降低ROS表达、抑制COX-2和HSP70表达和抑制NF-kB通路等来诱导细胞凋亡。当与干扰素联合使用时,其能阻碍血管生成。结论:尽管鞭檐犁头尖具有良好的抗癌活性,但其作为单独抗癌药物的疗效尚不确定。它似乎更适合用于癌症的补充或联合治疗。研究设计不理想,报告不完整,以及在多篇文章中没有纳入适当的阳性对照和统计分析可能是本研究缺乏结论性证据的原因。

摘要：New HPLC method was developed for determination of amlodipine and valsartan in their binary mixture as a part of routine control of combined formulations. The method was validated to meet official requirements including selectivity, stability, linearity, precision and accuracy. Chromatography was carried out using a LiChrospher RP-18 column, a mixture containing acetonitrile, phosphate buffer of pH 3.5 and methanol (45:45:10, v/v/v) and new fluorescence detection at 255 nm for excitation and 448 nm for emission. The effect of methanol content, pH of the buffer, flow rate, detection wavelengths and column temperature was estimated in robustness study, according to a plan defined by the Plackett-Burman design. For identification of significant effects, both graphical and statistical methods were used. Ro-bustness for dissolution test was checked estimating the effects of paddle speed, temperature and pH of dissolution medium. The method was proved to complying with all official guidelines. Therefore, it is suitable for determination of amlodipine and valsartan in their binary mixtures for different analytical and pharmaceutical purposes.

摘要：Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECM)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBMSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECM(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanofiller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBMSCs viability upon *** composite of human bone-ECM-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAM)*** inclusion of bone morphogenetic protein-2(BMP-2)with the HBMSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECM)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

摘要：Starting from 4,6-dimethyl-2-oxo-(1H)-3-pyridinecarbonitrile 1 and 3-aminopyrazolopyridine 4, a series of cyanopyri- dine derivatives 3a-i, Schiff bases 5a-f, urea and thiourea derivatives 6a-b, amide derivatives 7a-h, pyridopyra- zolopy-rimidine 8a-b and pyridopyrazolotriazine 10a-b were synthesized. Activities of eleven representative compounds were evaluated against A-549 (lung), HEPG2 (liver) and HCT-116 (colon) cancer cell lines. The findings revealed that some of the synthesized compounds showed remarkable anticancer activities, especially 8b which displayed the highest activity among the tested compounds with IC50 equal to 2.9, 2.6 and 2.3 μmol. In addition to synthesis and biological activities, we present discussion about the rationale of the design and activity of the potent compound 8b using struc- ture-based modeling tools.