Synthesis and antitumor activities of structure-related small molecular compounds of gambogic acid

Through simplifying the complicated skeleton of the natural product gambogic acid, two series derivatives of chromone and xanthone were synthesized and examined for their antitumor activities against several cancer cells in vitro by MTT method. The results showed that appropriate introduction of prenyl group to the small molecular compounds could elevate their antitumor activities. The structure–activities relationship of synthesized compounds certified that the bridgecore in gambogic acid was very important for keeping its antitumor activities.

Amphiphilic small molecular mates match hydrophobic drugs to form nanoassemblies based on drug-mate strategy

Nanomedicine has made great progress in the targeted therapy of cancer. Here, we established a novel drug-mate strategy by studying the formulation of nanodrugs at the molecular level. In the drug-mate combination, the drug is a hydrophobic drug that is poorly soluble in water, and the mate is an amphiphilic small molecule (SMA) that has both hydrophilic and lipophilic properties. We proposed that the hydrophobic drug could co-assemble with a suitable SMA on a nanoscale without additive agents. The proof-ofconcept methodology and results were presented to support our hypothesis. We selected five hydrophobic drugs and more than ten amphiphilic small molecules to construct a library. Through molecular dynamic simulation and quantum chemistry computation,we speculated that the formation of nanoassemblies was related to the binding energy of the drug-mate, and the drug-mate interaction must overcome drug-drug interaction.Furthermore, the obtained SF/VECOONa nanoassemblieswas selected as a model, which had an ultra-high drug loading content (46%), improved pharmacokinetics, increased bioavailability, and enhanced therapeutic efficacy. In summary, the drug-mate strategy is an essential resource to design exact SMA for many hydrophobic drugs and provides a reference for the design of a carrier-free drug delivery system.

Cytotoxic effect of a non-peptidic small molecular inhibitor of the p53-HDM2 interaction on tumor cells

AIM: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.METHODS: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors. Cytotoxic effect of syl-155 on three tumor cell lines with various states of p53, HT1080 (wild-type p53), KYSE510 (mutant p53), MG63 (p53 deficiency) was evaluated by MTT assay, Western blot and flow cytometry.RESULTS: Syl-155 stimulated the accumulation of p53 and p21 protein in HT1080 cells expressing wild-type p53, but not in KYSE510 and MG63 cells. Consequently, syl-155 induced cell cycle arrest and apoptosis in HT1080 cells.CONCLUSION: Non-peptidic small molecular inhibitors of the p53-HDM2 interaction show promise in treatment of tumors expressing wild-type p53.

High-performance asymmetric small molecular donor materials based on indenothiophene for solution-processed organic solar cells

Two novel asymmetric organic small molecules of IT(2FBT-T3Cz)_2and IT(2FBT-TT3Cz)_2with an indenothiophene(IT)central donor core,fluorinated benzothiadiazole(2FBT)as acceptor and 3-carbazole(Cz)unit as terminal group were designed and synthesized as the donor materials in organic solar cells(OSCs).The thermal,optical absorption,electrochemical property,hole–electron mobility,film morphology were thoroughly studied.Using PC_(71)BM as an electron acceptor,without any additive and thermal annealing(TA)treatment,the IT(2FBT-T3Cz)_2-based cells showed a promising power conversion efficiency(PCE)of5.81%and the IT(2FBT-TT3Cz)_2-based cells exhibited a PCE of 4.39%.Our results demonstrate that the IT-based asymmetric small molecules can be developed as a promising class of donor materials for highperformance OSCs.

Developing New Small Molecular Drugs for Prostate Cancer Therapy

Most of the early prostate cancer has no obvious symptoms, but its malignancy metastasis will cause largely deaths. The treatment options for patients with prostate cancer include traditional surgery, external beam therapy, hormone therapy, small molecular drug and cryosurgery. It was considered non-traditional treatments also can be used in alternative medicines for prostate cancer therapy. There are well-known molecular mechanisms and their pathogenesis, which provide potential targets for drug screening on the prostate cancer. Currently, natural plant extracts or human tissues active ingredients are widely used for the treatment of cancer. Then isolated effective substances in the extract, and further prepared large amounts of small molecule drugs by chemical synthesis. In this review, we summarized four small molecular drugs, abiraterone, docetaxel, isochaihulactone and butylidenephthalide, and their detailed anti-tumor mechanisms. These indicate that small molecular drug is a very efficient way and can be used for prostate cancer treatment.

Inner alkyl chain modulation of small molecular acceptors enables molecular packing optimization and efficient organic solar cells

With the generation of Y6,organic solar cells have reached remarkable achievement of over 19%efficiency.Alkyl chain is of importance to modulate intermolecular stacking and possibly enhance optoelectronic properties of small molecule acceptors(SMAs).Three alkyl chains of 2-ethylhexyl,2-butylocyl and 3-ethylheptyl were selected to obtain G6-EH,G6-BO and G6-EHep molecules,respectively.Compared to G6-EH and G6-BO,G6-EHep was found inducing unfavourable large domain size.Furthermore,we discover that 2-butyloctyl effectively inhibits monomolecular and bimolecular recombination,improves molecular packing,generates more balanced carrier mobility and enhances exciton dissociation.The SMA with 2-butyloctyl alkyl chains(G6-BO)shows the best electrical and morphological characteristics,achieving a higher power conversion efficiency(PCE)of 17.06%,with an open circuit voltage of 0.912 V,a short-circuit current of 24.22 m A cm-2and a fill factor of 77.25%.Finally,using the ternary strategy by incorporating the G6-BO acceptor into PM6:BTP-e C9,we achieved a higher PCE of18.13%with enhanced electron transport.

Wide Band Gap Non-Fullerene Small Molecular Acceptors Containing Spirobifluorene and Benzotriazole with Three Different End-Capped Groups for P3HT-Based Organic Solar Cells

Spirofluorene （SF） and benzo[d][1,2,3]triazole （BTA） have been considered as promising building blocks to construct n-type photovoltaic materials. Herein, three new small molecule acceptors （SMAs） named BTA21, BTA23 and BTA27 with the structure of A2=A1-D-AI^A2 have been designed, in which SF and BTA were used as a central unit of D and bridged acceptor unit of A1, respectively. In addition, 3-ethylrhodanine, 2-（3-ethyl-4-oxothiazolidin-2-ylidene）malononitrile and malononitrile were chosen as terminal acceptor units to modulate the properties of the final SMAs. Three SMAs show wide optical band gaps （Eg） of 2.19, 2.15 and 2.22 eV, respectively, with gradually down-shift of the lowest unoccupied molecular orbital {LUMO） levels in the order of BTAZl, BTA23 and BTA27 depending on the electron-withdrawing capability of terminal acceptor units. BTA21 shows great advantages with respect to donor poly（3-hexylthiophene） （P3HT） over BTA23 and BTA27, such as well energy-level matching, complementary absorption and proper morpholgy, Concequently, P3HT：BTA21 shows the best power conversion efficiency （PCE） value of 3.28% with an open-circuit voltage （Voc） of 1.02 V, a short-circuit current （Jsc） of 5.45 mA.cm-2 and a fill factor （FF） of 0.59. These results indicate that the terminal acceptor group end-capped in SMAs plays a significant role in controlling their optical, electronic, and photovoltaic properties.

Polymerizing small molecular acceptors for efficient all-polymer solar cells

All-polymer solar cells(all-PSCs)have received attention due to their morphological stability under thermal and mechanical stresses.Currently,the highest reported power conversion efficiency of all-PSCs is over 17%,achieved by utilizing polymerized small molecular acceptors(PSMAs).However,the need for higher regiospecificity to avoid forming isomers during polymerization of SMAs still challenges the further applications of all-PSCs.From this perspective,we focus on some recent studies and highlight the importance of controlling the regioregularity of PSMAs.In particular,integrating PSMAs with regioregularity endows the polymer acceptors with good absorption,superior backbone ordering,and optimal blend morphology compared with those obtained from regiorandom one.Moreover,the distinctive features that are derived from these regioregular PSMAs,such as the possibility of repeatable synthesis and reproducible device performance,herald a brighter future for scaling-up and commercializing all-PSCs.We expect this integrated strategy will inspire researchers to devote more efforts to further narrow the efficiency gap between the PSCs based on SMAs and PSMAs.Finally,we discuss the existing challenges and future prospects of PSMAs as new platform for further advancing all-PSCs.

Detection of Radical Adducts with Small Molecular Weights by Matrix-Assisted Laser Desorption/Ionization with Fourier Transform Mass Spectrometry

As an alternative method, matrix-assisted laser desorption/ionization with Fourier transform mass spectrometry （MALDI-FTMS） has been successfully used to detect and identify free radical adducts with small molecular weights of hydroxyl and 2-cyano-2-propyl radicals trapped with 5,5-dimethylpyrroline N-oxide （DMPO）. The detection and identification by MS/MS experiments using sustained offresonance irradiation collision-induced dissociation （SORI-CID） of [（DMPO＋·OH-·H）＋H^＋] （m/z 130.0868） and [DMPO＋2 ·CH（CH3）2CN＋H^＋] （m/z 250.1917） have demonstrated that MALDI-FTMS could be an effective method for detection and identification of free radical adducts. Other radical adducts have been also detected and identified. The approach of MALDI-FTMS is simple, fast, and sensitive which has potential for high-throughput analysis.

Self-assembled small molecular weight hydrogels of prodrugs

Molecular self-assembly is very ordinary phenomenon in the biological process such as protein folding,DNA encoding and etc.Inspired by this inherent biological process,nanostructure such as nanofibers,nanosphere,and so on formed by the therapeutic agents and its derivatives that can further self-assemble into supramolecular hydrogels have attained considerable attentions in the field of drug delivery due to its favorable features such as high and precise drug payload,carrier-free and excellent biocompatibility.Additionally,the prodrug hydrogelator can be rationally designed to fine-tune over its drug release behavior and degradation in response to various biological stimulus（temperature,p H,ionic strength and etc.）.This review summarized and discussed the recent advancement in the self-assembled small molecular weight hydrogels of prodrugs.

Erlotinib Analogue-substituted Zinc（Ⅱ） Phthalocyanines for Small Molecular Target-based Photodynamic Cancer Therapy

＂Smart＂ targeted photosensitizer conjugated with small molecule target-based anticancer drug which has a sim- ple chemical structure and high stability, is a new promising targeted therapeutic strategy. We herein extended this strategy and reported a novel series of zinc（II） phthalocyanine-erlotinib analogue conjugates with different periph- eral substituted positions and lengths of the linker. Having erlotinib analogue as the targeting moiety, all conjugates exhibited high specificity and potent affinity to HepG2 cancer cells and kept high photodynamic activity （ICs0 = 3.7 -- 16.7 nmol/L）. Structure-activity relationships of these conjugates were assessed by investigating their photophys- ical/photochemical properties, targeting intracellular uptake and in vitro phototoxicity. The results suggested that a-substituted conjugates showed slightly higher photodynamic activity than ,8-substituted ones. In conclusion, we have developed a series of promising anticancer agents with high tumor selectivity and anticancer activity for targeted photodynamic therapy.

Effects of subtle change in side chains on the photovoltaic performance of small molecular donors for solar cells

Small-molecule organic solar cells(SMOSCs)have attracted considerable attention owing to the merits of small molecules,such as easy purification,well-defined chemical structure.To achieve high-performance SMOSCs,the rational design of well-matched donor and acceptor materials is extremely essential.In this work,two new small molecular donor materials with subtle change in the conjugated side thiophene rings are synthesized.The subtle change significantly affects the photovoltaic performance of molecular donors.Compared with chlorinated molecule MDJ-Cl,the non-chlorinated analogue MDJ exhibits decreased miscibility with the non-fullerene acceptor Y6,can more efficiently quench the excitons of Y6.As a result,a improved PCE of 11.16% is obtained for MDJ:Y6 based SMOSCs.The results highlight the importance of fine-tuning the molecular structure to achieve high-performance SMOSCs.

Enhancement of morphological and emission stability of deep-blue small molecular emitter via a universal side-chain coupling strategy for optoelectronic device

Film morphology of emissive layers is crucial to the performance and stability of solution-processable organic light-emitting diodes(OLEDs). Compared to the interpenetration of conjugated polymer chain,small molecular emitter with a flexible side chain always presents easily aggregation upon external treatment, and caused π-electronic coupling, which is undesirable for the efficiency and stability of deep-blue OLEDs. Herein, we proposed a side-chain coupling strategy to enhance the film morphological an emission stability of solution-processable small molecular deep-blue emitter. In contrary to “parent” MC8 TPA,the crosslinkable styryl and vinyl units were introduced as ended unit at the side-chain of Cm TPA and OEYTPA. Interestingly, Cm TPA and OEYTPA films present a relatively stable morphology and uniform deep-blue emission after thermal annealing(160 ℃) in the atmosphere, different to the discontinuous MC8 TPA annealed film. Besides, compared to the Cm TPA and OEYTPA ones, serious polaron formation in the MC8 TPA annealed film also negative to the deep-blue emission, according to transient absorption analysis. Therefore, both Cm TPA and OEYTPA annealed film obtained at 140 ℃ present an excellent deep-blue ASE behavior with a 445 nm, but absence for MC8 TPA ones, associated with the disruption of annealed films. Finally, enhancement of device performance based on Cm TPA and OEYTPA film(~40%)after thermal annealing with a similar performance curves also confirmed the assumption above. Therefore, these results also supported the effectiveness of our side-chain coupling strategy for optoelectronic applications.

Small Molecular NIR-II Fluorophores for Cancer Phototheranostics

Phototheranostics integrates deep-tissue imaging with phototherapy(containing photothermal therapy and photodynamic therapy),holding great promise in early diagnosis and precision treatment of cancers.Recently,second near-infrared(NIR-II)fluorescence imaging exhibits the merits of high accuracy and specificity,as well as real-time detection.Among the NIR-II fluorophores,organic small molecular fluorophores have shown superior properties in the biocompatibility,variable structure,and tunable emission wavelength than the inorganic NIR-II materials.What’s more,some small molecular fluorophores also display excellent cytotoxicity when illuminated with the NIR laser.This review summarizes the progress of small molecular NIR-II fluorophores with different central cores for cancer phototheranostics in the past few years,focusing on the molecular structures and phototheranostic performances.Furthermore,challenges and prospects of future development toward clinical translation are discussed.

New developments in small molecular compounds for anti-hepatitis C virus(HCV) therapy

Infection with hepatitis C virus(HCV) affects approximately 170 million people worldwide.However,no vaccine or immunoglobulin is currently available for the prevention of HCV infection.The standard of care(SOC) involving pegylated interferon-α(PEG-IFN α) plus ribavirin(RBV) for 48 weeks results in a sustained virologic response in less than 50% of patients with chronic hepatitis C genotype 1,the most prevalent type of HCV in North America and Europe.Recently,reliable in vitro culture systems have been developed for accelerating antiviral therapy research,and many new specifically targeted antiviral therapies for hepatitis C(STAT-C) and treatment strategies are being evaluated in clinical trials.These new antiviral agents are expected to improve present treatment significantly and may potentially shorten treatment duration.The aim of this review is to summarize the current developments in new anti-HCV drugs.

Hematopoietic effect of small molecular fraction of Polygoni multiflori Radix Praeparata in cyclophosphamide-induced anemia mice

The aim of this study is to investigate the protective effects of a small molecular fraction(SMF) of Polygoni multiflori Radix Praeparata(PMRP) in a cyclophosphamide(CTX) induced anemia mouse model. Small molecular fraction of PMRP was prepared and identified by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(HPLC-Q-TOF-MS). In pharmacology, we examined the peripheral hemogram and thymus and spleen index. The content of granulocyte-macrophage colony-stimulating factor(GM-CSF) in serum was mensurated by enzyme-linked immunosorbent assay(ELISA);The level of superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), and malondialdehyde(MDA) in serum and spleen tissue homogenate were detected, and glutathione peroxidase(GSH-PX) was assayed in spleen. The results show that SMF can significantly accelerate the recovery of peripheral hemogram, increase the activity of antioxidant enzymes and GM-CSF in serum and spleen. SMF also increases the number of spleen cells, improves bone marrow pathology. In conclusion, the SMF of PMRP promoted the recovery of hematopoietic function in a CTX-induced anemia mouse, which can support SMF to be used as an adjunct to chemotherapy to counteract its side effects.

A small molecular electron acceptor based on asymmetric hexacyclic core of thieno[1,2-b]indaceno[5,6-b']thienothiophene for efficient fullerene-free polymer solar cells

A novel A-D-A(acceptor-donor-acceptor)type non-fullerene small molecule,A201,consisting of an asymmetric thieno[1,2-b]indaceno[5,6-b^0]thienothiophene(TITT)unit as middle D part and 2-(3-oxo-2,3-dihydroinden-1-ylidene)malononitrile(IC)groups as end-capped A parts was designed and synthesized.The asymmetric TITT building block showed a higher dipole moment of 0.85 Debye(1 Debye=3.33564?10^(à30)cm)compared with the symmetric analogues of indacenodithiophene(IDT)and indacenodithieno[3,2-b]thiophene(IDTT)of 0.098 and 0.13 Debye,respectively.The solution-processed bulk heterojunction solar cells using a benzotriazole(BTA)-based polymer of J71 as donor and A201 as acceptor,showed a power conversion efficiency(PCE)of 9.36%with an open-circuit voltage(V_(oc))of0.88 V,a short-circuit current(J_(sc))of 13.15 m A cm^(à2),and a fill factor(FF)of 0.67,under the illumination of AM 1.5G at 100 m W cm^(à2).The high PCE of this material combination could be attributed to its broad absorption spectrum and the high hole mobility(l_h)and electron mobility(l_e)of 9.56?10^(à4)and 5.17?10^(à4)cm^2V^(à1)s^(à1),respectively.These results indicate that the asymmetric electron-donating segments are promising to construct A-D-A type small molecular acceptors,which could largely enhance the diversity of building blocks to design photovoltaic materials.

Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

Non-small-cell lung cancer(NSCLC)remains the leading cause of cancer-related death in both men and women in the United States.Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease.Improvements in overall survival and quality of life have been modest.Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics,thus changing the treatment paradigm for many NSCLC patients.In this review,we present a summary of many of the currently investigated biologic targets in NSCLC,discuss their current clinical trial status,and also discuss the potential for development of other targeted agents.

沙蚕运动饮料的制备及其对小鼠运动耐力的影响

以双齿围沙蚕小分子酶解产物(小于5 kDa)作为原料研制沙蚕运动饮料。通过考察不同辅料、不同含量的沙蚕小分子酶解产物、不同的灭菌方式对饮料DPPH自由基清除作用的影响并结合感官评价确定沙蚕运动饮料的最佳配方,并探究沙蚕运动饮料的抗疲劳功效。实验结果表明,沙蚕运动饮料的最佳配方为沙蚕小分子酶解产物(小于5 kDa)含量40%、白砂糖含量5%、罗汉果多糖含量0.02%、柠檬汁含量1.2%、磷酸二氢钾含量0.05%、磷酸二氢钠含量0.1%、NaCl含量0.05%(均为质量分数),其(质量浓度为2.25 mg/mL)DPPH自由基的清除率为94.1%,IC_(50)值为0.8 mg/mL;动物实验结果显示,高剂量沙蚕运动饮料可显著(P<0.01)延长小鼠的负重游泳时间,低、中、高剂量沙蚕运动饮料均能显著增加小鼠肝糖原的含量(P<0.01)并能显著降低小鼠血清尿素氮含量(P<0.01),同时低剂量沙蚕运动饮料能显著降低小鼠血乳酸的含量(P<0.01),具有显著的抗疲劳功效。

猴头菌培养液乙酸乙酯提取物的化学成分研究

目的研究猴头菌培养液乙酸乙酯提取物的化学成分。方法通过凝胶柱色谱、硅胶柱色谱、半制备高效液相色谱等技术进行分离和纯化;根据其理化性质数理和波谱对得到的化合物进行结构鉴定。结果从猴头菌培养液乙酸乙酯提取物中分离并鉴定得到22个化合物,分别为3-甲氧基-4-羟基苯甲醛(1),吲哚甲酸甲酯(2),2-呋喃甲酸(3),苯甲酸(4),2(3H)-苯并恶唑酮(5),香草酸(6),没食子酸(7),polisin C(8),bis(2-ethylhexyl)benzene-1,2-dicarboylate(9),p-tyrosyl acetate(4-hydroxyphenethyl acetate)(10),1-(4-hydroxy-3,5-dimethoxyphenyl)ethanon(11),对羟基苯乙酮(12),1-苯基-1,2-丙二醇(13),6-羟基异苯并呋喃-1(3H)-酮(14),对羟基苯乙醛(15),1H-吲哚-3-吡咯甲醛(16),环(脯氨酸-缬氨酸)(17),环(脯氨酸-亮氨酸)(18),环(苯丙氨酸-缬氨酸)(19),环(异亮氨酸-苯丙氨酸)(20),苜蓿素(21),dihydro-4-hydroxy-2(3H)-furanone(22)。结论除化合物16和21外,其他化合物均为首次从猴头菌培养液中分离得到。