摘要：As epoxy functional group has high anticancer activity, α, β-epoxyketones were designed and synthesized as new anticancer agents, and their structures were confirmed by UV, 1H NMR, IR, MS technigeces and elemental analysis. Their in vitro anticancer activities were evaluated by MTF method and the results showed that the compound 4c exhibited good activity with IC50 of 17.8, 22.0 and 24.1 μg/mL against A-549, Hela and HepG2 cells, respectively. The dose of LD50 of the mice by intragastric administration was 1864.4 mg/kg. Therefore, the α, β-epoxyketones could potentially provide as new anticancer agents.

摘要：A series of 3-substituedmethylenethiochroman-4-ones was designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR, MS, IR, UV and elemental analysis. The results of their anticancer activity studies show that almost all 3-chloromethylenethiochroman-4-ones exhibit high anticancer activities and their activities are all better than reference cisplatin. Their IC50 against cancer cells is in a range of 0.80―9.17 μg/mL. Thus they could be promising candidates for anticancer drugs. However, compound 5 has no activity against cancer cells, thus chloromethylene at the 3 position of thiochroman-4-ones seems to play an important role in observed anticancer activities.

摘要：The eyes present unique opportunities and challenges when it comes to the delivery of *** absorption by this route is bungling,there are a few side effects with conventional dosage *** inserts were prepared with prolonged release of drug and minimum swelling within cul-de-sac using *** work focused on treatment of conjunctivitis and cataracts by formulating ocular inserts of different polymeric combination of aceclofenac using hydroxypropyl methyl cellulose(HPMC,3% to 5%),chitosan(3% to 5%),poly vinyle alcohol(PVA,3% to 5%),methyl cellulose(MC,3% to 5%) as drug reservoir and ethyl cellulose(EC) polymer as rate controlling membrane by solvent casting technique with the objective of increasing contact time,achieving controlled release and greater therapeutic *** prepared ocular insert were then evaluated for physical appearances tensile strength,elongation at break(%),weight variation,uniformity of thickness,moisture absorption(%),pH,folding endurance,Fourier Transform Infrared spectroscopy,differential scanning *** characterization and in vitro transcorneal permeation studies reveals that,the prepared ocular insert formulations F2 and F8 containing HPMC and PVA had released their drug content,98.54% and 96.24%,respectively,over an extended period of 24 *** these formulations were selected as best optimized *** can be concluded that hydroxy propyl methyl cellulose is a good film forming hydrophilic polymer which shows potential agent for ocular drug delivery *** of polyethylene glycol enhances the permeability of aceclofenac ocular insert and has perfect zero order release,proving a promising controlled release delivery system.

摘要：4,5-Dihydro-3-methylbenzo[1,2-b]furan-4,5-dione（4） was identified as a novel and potent inhibitor of caspase-3 through structural modification of an existing drug, sodium tanshinone IIA sulfonate（STS）. Compound 4 showed high potency against caspase-3 in vitro（ICso=0. 13μmol/L）. Molecular docking study further provided an insight into the interaction of compound 4 with activated caspase-3. Hence, this small-molecule caspase-3 inhibitor could be a oromising theraoeutic candidate against diseases caused by abnormally up-regulated apptosis.

摘要：In this paper,we present a 3D printed tumor spheroidal model suitable for drug *** model is based on a hydroxyethyl cellulose/alginate/gelatin(HCSG)composite biomaterial that has three distinct properties:(1)the HCSG is similar to the commercial basement membrane extract in Ki67,MUC1,and PARP1 expressions of MCF-7 cells for embedding culture;(2)the HCSG is printable at room temperature;and(3)the HCSG can be large-scale manufactured at an ultralow *** printed a 3D MCF-7 spheroid model with HCSG and characterized it in terms of cell viability,spheroid size,key protein expression,and mitochondrial metabolic *** used the 3D MCF-7 spheroid model to evaluate the anti-breast cancer activity of 13 amino acid-based flavone phosphoramidates and found that the alanine structure induced a stronger drug resistance,whereas phenylalanine hardly caused drug resistance in the MCF-7 *** is the first time that 3D bioprinting technology has been used in a structure–activity relationship study.

摘要：The differential distribution between cancer cells and normal adult tissues makes survivin a very attractive cancer drug target. We have previously reported a series of novel selective survivin inhibitors with the most potent compound MX 106 reaching nanomolar activity in several cancer cell lines. Further optimization of the MX 106 scaffold leads to the discovery of more potent and more selective survivin inhibitors. Various structural modifications were synthesized and their anticancer activities were evaluated to determine the structure activity relationships for this MX 106 scaffold. In vitro anti-proliferative assays using two human melanoma cell lines showed that several new analogs have improved potency compared to MX 106. Very interestingly, these new analogs generally showed significantly higher potency against P-glycoprotein overexpressed cells compared with the corresponding parental cells, suggesting that these compounds may strongly sensitize tumors that have high expressions of the Pglycoprotein drug efflux pumps. Western blotting analysis confirmed that the new MX 106 analogs maintained their mechanism of actions by selectively suppressing survivin expression level among major inhibitors of apoptotic proteins and induced strong apoptosis in melanoma tumor cells.

摘要：A new series of benzamide derivatives as glucokinase activators （GKAs） were designed and synthesized, and their activation for glucokinase were evaluated by the preliminary glucokinase activity assay. The structure-activity relationship （SAR） is discussed. The result shows that compound 12d and 12h have potent activity reference drug RO-28-1675.

摘要：Chitosan,a natural cationic polysaccharide,is prepared industrially by the hydrolysis of the aminoacetyl groups of chitin,a naturally available marine *** is a non-toxic,biocompatible and biodegradable polymer and has attracted considerable interest in a wide range of biomedical and pharmaceutical applications including drug delivery,cosmetics,and tissue *** primary hydroxyl and amine groups located on the backbone of chitosan are responsible for the reactivity of the polymer and also act as sites for chemical ***,chitosan has certain limitations for use in controlled drug delivery and tissue *** limitations can be overcome by chemical ***,modified chitosan hydrogels have gained importance in current research on drug delivery and tissue engineering *** paper reviews the general properties of chitosan,various methods of modification,and applications of modified chitosan hydrogels.

摘要：CThe objective of the present study was to prepare solid self-nanoemulsifying drug delivery system(S-SNEDDS)containing Capryol-90 as oil phase for the delivery of Embelin,a poorly water soluble herbal active ***-Behnken experimental design was employed to optimise the formulation variables,X1(amount of oil;Capryol 90),X2(amount of surfactant;Acrysol EL 135)and X3(amount of co-surfactant;PEG 400).Systems were appraised for visual characteristics for self emulsifying time,globule size and drug *** liquid formulations were formulated into free flowing granules(S-SNEDDS)by adsorption on the porous materials like Aerosil 200 and Neusilin and thereby compressed into *** vitro dissolution studies of SNEDDS revealed increased in the dissolution rate of the ***-IR data revealed no physicochemical interaction between drug and *** state characterization of S-SNEDDS by DSC and Powder XRD confirmed reduction in drug crystallinity which further supports the results of dissolution *** analysis exhibited spherical ***,the accelerated stability studies for 6 months revealed that S-SNEDDS of Embelin are found to be stable without any significant change in physicochemical ***,the present studies demonstrated dissolution enhancement potential of porous carrier based S-SNEDDS for poorly water soluble herbal active ingredient,Embelin.

摘要：This is a brief review of the computational modeling of protein-ligand interactions using a recently developed fully polarizable continuum model(FPCM)and rational drug *** modeling has become a powerful tool in understanding detailed protein-ligand interactions at molecular level and in rational drug *** study the binding of a protein with multiple molecular species of a ligand,one must accurately determine both the relative free energies of all of the molecular species in solution and the corresponding microscopic binding free energies for all of the molecular species binding with the *** this paper,we aim to provide a brief overview of the recent development in computational modeling of the solvent effects on the detailed protein-ligand interactions involving multiple molecular species of a ligand related to rational drug *** particular,we first briefly discuss the main challenges in computational modeling of the detailed protein-ligand interactions involving the multiple molecular species and then focus on the FPCM model and its *** FPCM method allows accurate determination of the solvent effects in the first-principles quantum mechanism(QM)calculations on molecules in *** combined use of the FPCM-based QM calculations and other computational modeling and simulations enables us to accurately account for a protein binding with multiple molecular species of a ligand in *** on the computational modeling of the detailed protein-ligand interactions,possible new drugs may be designed rationally as either small-molecule ligands of the protein or engineered proteins that bind/metabolize the *** computational drug design has successfully led to discovery and development of promising drugs.