Deeper Chemical Perceptions for Better Traditional Chinese Medicine Standards

Traditional Chinese medicines (TCMs), a complex system of natural resources with many diverse components, are widely used as approved medicinal agents in China. Quality control of TCMs is a huge challenge for the government and for testing institutes and is associated with numerous scientific issues. Among these considerations include the following questions: How many components are in TCMs? How can the multiple components in TCMs be comprehensively delineated and subsequently characterized? What is the level and range of these (active) metabolites within these multiple-component TCMs, in order to recommend standards? and What are the qualities required for a marker constituent to be selected, and from a practical perspective, how can these components be assessed with low cost and in a short time? All of these factors require significant and deep thinking in order to understand the individualistic chemistry of TCM in order to develop enhanced TCM quality standards for improved and consistent patient care. In this review, the latest exploratory research in TCM chemistry analytical techniques and methods is summarized in order to begin to develop responses to these scientific issues. Advances in these methods have included multidimensional separation for liquid chromatography–high-resolution mass spectrometry (LC–HRMS), smart triggering data-dependent acquisition of LC–HRMS, target analysis with liquid chromatography–mass spectrometry (LC–MS), supercritical fluid chromatography, and data mining of large mass spectrometry (MS) datasets. In addition, two quality strategies have been introduced in order to save reference standards and the analysis time for a TCM quality standard, including the application of the single standard to determine multi-components (SSDMC) and monomethodheterotrait matrix methods. Finally, a series of future improvements for analytical methods for TCMs are proposed.

TDZ-Induced High Frequency Plant Regeneration through Direct Shoot Organogenesis in <i>Stevia rebaudiana</i>Bertoni: An Important Medicinal Plant and a Natural Sweetener

An efficient high frequency plant regeneration protocol through direct organogenesis was developed for Sevia rebaudiana Bert. Nodal segments containing axillary buds were used as an explant and inoculated on Murashige and Skoog’s (MS) medium containing 3% (w/v) sucrose, 0.8% (w/v) agar supplemented with various concentrations of benzyladenine (BA), kinetin (Kn) and thidiazuron (TDZ) ranging from 1.00 to 9.00 μM. Maximum multiple shoots (96%) were obtained in MS medium supplemented with 1.0 μM TDZ with an average of 60 shoots per culture, having an average shoot length of 6.0 cm. The best in vitro root induction (89%) was achieved on half strength MS medium without any growth regulator with an average of 24 roots per culture and root length of7 cm. The rooted plantlets were successfully established in soil and grown to maturity at the survival rate of 95% in the indoor grow room. High-performance liquid chromatography was used to assess the stability in chemical profile and quantification of stevioside and rebaudioside A content of in vitro propagated S. rebaudiana plants and compared with their mother plant at the peak vegetative stage. Our results show no significant differences (p in vitro propagated plants. Furthermore, fully developed in vitro propagated S. rebaudiana plants were also compared with mother plant for their gas and water vapour exchange characteristics and leaf anatomy. The results show that in vitro propagated and hardened plants of S. rebaudiana are morphologically as well as functionally comparable to each other and to their mother plant.

PGRMC1 Elevation in Multiple Cancers and Essential Role in Stem Cell Survival

Cancer is one of the leading causes of death in America, and there is an urgent need for new therapeutic approaches. The progesterone receptor membrane component 1 (PGRMC1) is a cytochrome b5 related protein that binds heme and is associated with signaling, apoptotic suppression and autophagy. PGRMC1 is essential for tumor formation, invasion and metastasis, and is upregulated in breast, colon, lung and thyroid tumors. In the present study, we have analyzed PGRMC1 levels in over 600 tumor sections, including a larger cohort of lung tumors than in previous studies, and report the first clinical analysis of PGRMC1 levels in human oral cavity and ovarian tumors compared to corresponding nonmalignant tissues. PGRMC1 was highly expressed in lung and ovarian cancers and correlated with patient survival. PGRMC1 has been previously associated with drug resistance, a characteristic of cancer stem cells. The stem cell theory proposes that a subset of cancerous stem cells contribute to drug resistance and tumor maintenance, and PGRMC1 was detected in lung-tumor derived stem cells. Drug treatment with a PGRMC1 inhibitor, AG-205, triggered stem cell death whereas treatment with erlotinib and the ERK inhibitor, PD98059, did not, suggesting a specific role for PGRMC1 in cancer stem cell viability. Together, our data demonstrate PGRMC1 as a potential tumor biomarker across a variety of tumors, as well as a therapeutic target for cancer stem cells.

Green Plant Protection Innovation: Challenges and Perspectives

This issue of Engineering was compiled from papers presented at the First International Conference on Green Plant Protection Innovation(1st ICGPPI),held in Haikou in May 2018,and the Second International Conference on Green Plant Protection Innovation(2nd ICGPPI),held in Guiyang in October 2019.The conferences were sponsored by the Chinese Academy of Engineering,and the Academic Committee of the Forum of the ICGPPI,chaired by Professor Baoan Song,organized the conference.The 1st ICGPPI was attended by more than 800 people from seven countries,while the 2nd ICGPPI had more than 200 attendees from nine countries.The wide range of topics related to more environmentally sound crop protection was of great interest to all,and the meetings provided provided an opportunity for scientists from many disciplines of crop protection to exchange and share ideas and advances.

Isolation of antileishmanial,antimalarial and antimicrobial metabolites from Jatropha multifida

Objective:To investigate the antileishinanial,antimicrobial and antimalarial activities of the pure metabolites from Jatropha multifida used in African ethnomedicine.Methods:The methanolic stem bark extract of Jatropha multifida used in Nigerian folk medicine as remedy against bacterial infections was subjected to column chromatography and HPLC analyses lo obtain three known metabolites,microcyclic lathyrane dilerpenoids(1-3).Structures were confirmed by comparison of 1D and 2D spectral data with literature.Results:The three compounds exhibited inhibition of antileishmanial,antimalarial and antimicrobial actions against the tested organisms with compouds 2 and 3 active against Cryptococcus neoformans at IC_(50)of 82 and 8.7 μg/ml,respectively.Conclusions:The research lends support to the ethnomedicinal use of the plant in combating microbial infections,leishmaniasis and malarial infections.

An Investigation of the Vegetative Anatomy of <i>Piper sarmentosum</i>, and a Comparison with the Anatomy of <i>Piper betle</i>(Piperaceae)

This paper describes the detailed anatomy and micromorphology of the vegetative parts of Piper sarmentosum Roxb. (synonym, P. lolot C.DC.), which is a southeast Asian medicinal plant valued for its medicinal and culinary uses. The study also compares the anatomy of the leaf, petiole, stem and root of P. sarmentosum with those of the well-characterized P. betle L. The leaves of both the species are morphologically comparable and have similar culinary uses. The present study showed that the leaves of both the species possess more or less comparable anatomical features with a few differences;whereas, the microscopic features of the petiole, stem, and root of the two species are distinctive.

Advance in Studies on Chemical Constituents, Pharmacology and Quality Control of Aquilaria sinensis

Aquilaria sinensis(Thymelaeaceae)is widely cultivated in southern China for its significant medicinal usage.The resinous wood,the most used part of the plant as traditional Chinese medicine(TCM),locally called“Chen Xiang(沉香)”or Chinese agarwood,has been traditionally used for the treatment of circulatory disorders,abdominal pain,vomiting,and dyspnea.Till date,over 249 compounds have been isolated and identified from this plant.A range of bioactivities,including α-glucosidase inhibitory effects,anti-inflammatory,cytotoxicity,neuroprotective,anti-neuroinflammatory,antimicrobial and acetylcholinesterase inhibitory effects,along with some of the pharmacological mechanisms have been reported for the pure compounds or extracts of Aquilaria sinensis.For the purpose of quality control and clinical safety of drug usage,modern analytical instruments and chemical analysis methods have been applied for analyses of Aquilaria sinensis.In order to comprehensively understand the medicinal application and to fully utilize the plant,a literature search on the herb based on databases including SciFinder,Web of Science,Pubmed,Google Scholar and others was performed and the information regarding to the phytochemistry investigations,pharmacological studies and quality control was summarized in this paper.

Antibacterial compounds from Rutaceae with activities against Flavobacterium columnare and Streptococcus iniae

From the ethyl acetate extract of Murraya koenegii (Rutaceae) leaves, isomahanine (1) and mahanine (2) were isolated that showed antibacterial activity towards Flavobacterium columnare and Streptococcus iniae which caused columnaris disease and streptococcosis respectively. Isomahanine was found to have the strongest activity against F. columnare (isolate ALM-00-173) and S. iniae (isolate LA94-426) based on 24-h 50% inhibition concentration (IC50) and minimum inhibition concentration (MIC). Although compound (7), a nicotinamide isolated from Amyris texana had the lowest MIC (2.8 ± 0 mg/L) of any of the test compounds against F. columnare, the 24-h IC50 of 14.8 ± 0.6 mg/L was higher than that of isomahanine and subsequently the 24-h IC50 RDC values for (7) were almost a magnitude of order higher than those obtained for isomahanine. Isomahanine also had the strongest activity against S. iniae, with a 24-h IC50 of 1.3 ± 0.1 mg/L and MIC of 3.5 ± 0 mg/L, respectively.

Safflower (Carthamus Tinctorius L.) a Potential Source of Drugs against Cryptococcal Infections, Malaria and Leishmaniasis

In this research we present that Carthamus Tinctorius L.(gen.Asteraceae,otherwise known as Safflower)(Fig.1)may contain agents active in Cryptococcal infections,malaria and Leishmaniasis,as treatment options are becoming scarce due to drug resistance development.Phytochemistry and pharmacological activities(antimicrobial,antimalarial,antileishmanial)of C.tinctorius L.were analyzed.The composition of volatile oil of safflower dried flowers was analyzed by gas chromatography-mass spectrophotometry with flame ionization detector(GC-FID)and in vitro sensitivity assays were performed to assess biological activity.8 known and 3 unknown compounds were detected in the extract(Fig.1).Then the Safflower ointment was manufactured and its acute toxicity study on rats was tested.The volatile oil of C.tinctorius L exhibited activity against Cryptococcus neoformans,Plasmodium falciparum and Leishmania donovani.Safflower volatile oil has anticryptococcal,antimalarial and antileishmanial effects.The prepared ointment had an excellent acute toxicity safety profile.

Analysis of docosanol using GC/MS:Method development,validation,and application to ex vivo human skin permeation studies

Docosanol is the only US Food and Drug Administration(FDA)approved over-the-counter topical product for treating recurrent oral-facial herpes simplex labialis.Validated analytical methods for docosanol are required to demonstrate the bioequivalence of docosanol topical products.A gas chromatography/selected ion monitoring mode mass spectrometry(GC/SIM-MS)method was developed and validated for docosanol determination in biological samples.Docosanol and isopropyl palmitate(internal standard)were separated on a high-polarity GC capillary column with(88%cyanopropy)aryl-polysiloxane employed as the stationary phase.The ions of m/z 83 and 256 were selected to monitor docosanol and isopropyl palmitate,respectively;the total run time was 20 min.The GC/SIM-MS method was validated in accordance with US FDA guidelines,and the results met the US FDA acceptance criteria.The docosanol calibration standards were linear in the 100-10000 ng/mL concentration range(R^(2)>0.994).The recoveries for docosanol from the receptor fluid and skin homogenates were>93.2%and>95.8%,respectively.The validated method was successfully applied to analyze ex vivo human cadaver skin permeation samples.On applying Abreva®cream tube and Abreva®cream pump,the amount of docosanol that penetrated human cadaver skin at 48 h was 21.5±7.01 and 24.0±6.95 ng/mg,respectively.Accordingly,we concluded that the validated GC/SIM-MS was sensitive,specific,and suitable for quantifying docosanol as a quality control tool.This method can be used for routine analysis as a costeffective alternative to other techniques.

Two new eudesmane derivatives from Verbesina virginica

Two new eudesmane derivatives were isolated from the leaves and flowers of Verbesina virginica,along with the known 6-O-β-E -p-coumaroyl-4α-hydroxyeudesmane(1).Their structures were determined as 6-O-β-Z-p-coumaroyl-4α-hydroxyeudesmane(2) and 6-O-α-E-p-coumaroyl-1β-4α-dihydroxyeudesmane(3) by spectroscopic methods.

Molecular Analysis of Genetic Fidelity in Micropropagated Plants of <i>Stevia rebaudiana</i>Bert. Using ISSR Marker

Inter-simple sequence repeat (ISSR) markers were used to evaluate the genetic fidelity of in vitro propagated and hardened plants of Stevia rebaudiana Bert. Nodal segments containing axillary buds were used as explant and inoculated on Murashige and Skoog’s (MS) medium containing 3% (w/v) sucrose, 0.8% (w/v) agar supplemented with various concentrations of benzyladenine (BA), kinetin (Kn) and thidiazuron (TDZ) ranging from 0.20 to 2.00 mg·L-1. Maximum multiple shoots (93%) were obtained in MS medium supplemented with 0.20 mg L-1 TDZ. The best in vitro root induction (87%) was achieved on half strength MS medium without any growth regulator. The rooted plantlets were successfully established in soil and grown to maturity at the survival rate of 96% in the indoor grow room. For ISSR analysis, total genomic DNA was extracted from 20 mg fresh leaves of mother and randomly selected in vitro propagated plants. Out of? fifteen arbitrary primers tested, each produced clear and scorable amplification products ranged in size from about 216 bp in UBC 811 to 1917 bp in (GGGGT)3M with an average of 4.5 products per primer. A total of 45 bands (number of plantlets analyzed multiplied by number of bands with all primers) were generated by the ISSR method. All the ISSR profiles from micropropagated plants were monomorphic and comparable to mother plants, confirming the genetic stability among micropropagated plants and mother plant. Chemical analysis, using high-performance liquid chromatography (HPLC), was done to further confirm the existence of qualitative and quantitative differences in the major secondary metabolites (rebaudioside A, stevioside and steviolbioside) between the mother plant and in vitro propagated plants. Our results clearly show similar chemical profiles and insignificant differences in the major secondary metabolites between the two types of plants. These results suggest that the micropropagation protocol followed in this study is appropriate and applicable for clonal mass propagation of true-to-type elite Stevia rebaudiana plants.

Bacterial Community Associated with Autotrophic and Heterotrophic Cultures of Medicinal Plant Smallanthus sonchifolius (Yacon)

Several unfruitful attempts to grow axenic shoot cultures of Smallanthus sonchifolius, also known as yacon, were made before healthy shoots grew in association with bacteria on half strength Murashigue and Skoog media supplemented with 2.2 μM benzylaminopurine. Twenty-one bacterial isolates were obtained from in vitro S. sonchifolius plantlets, eight of these isolates were identified as Flavimonas oryzihabitans, Curtobacterium pusillum, Sphingomonas paucimobilis, and Microbacterium imperiale. These microorganisms produced indole acetic acid (IAA) at amounts varying between 8.89 to 47.45 μg/mL, reason for being classified as plant growth promoting bacteria (PGPB). The results show that buds associated with bacteria cultured on sucrose free media produced 3.77 new roots measuring 18.33 cm in length after a 30-day growing period. In contrast, buds growing on sucrose supplemented media, the number of roots induced was higher (6.67 to 14 roots/explant) but shorter in length, 4.67 to 5.83 cm. During plant acclimatization to soil, photosynthesis and water efficiency were measured showing that the plants were healthy and vigorous. A slightly higher rate of photosynthesis and water use efficiency was recorded in the plants produced on heterotrophic conditions as compared to plants grown in sucrose free media. Plants adapted well in the soil demonstrating that the PGPB community associated to S. sonchifolius in shoot cultures was not harmful to plant production. The purpose of this study was to demonstrate that the bacteria associated with in vitro S. sonchifolius shoot cultures was not the result of microbial contamination, but rather from symbiotic associations that extended from cultivation in the greenhouse, to culture and back to soil. This is the first report to show that autotrophic cultures may represent a viable alternative to grow healthy plants without eliminating beneficial bacteria associated with the host.

Diversity and Biological Activities of Endophytic Fungi Associated with Micropropagated Medicinal Plant <i>Echinacea purpurea</i>(L.) Moench

Echinacea is one of the top ten selling medicinal herbs in Europe and United States. Commercially available formulations may contain different plant parts of three species (Echinacea purpurea, E. pallida, and E. angustifolia). Our study evaluates the diversity of microbial community associated with healthy E. purpurea clones and their ability to produce defense compounds. We recovered and identified thirty-nine fungal endophytes through the molecular methods in 15 distinct phylotypes, which were closely related to species of the following genera Ceratobasidium, Cladosporium Colletotrichum, Fusarium, Glomerella, and Mycoleptodiscus. These taxa were previously reported as decomposer and phytopathogenic fungi. The fungal community associated with two E. purpurea clones showed high richness and dominance indices with different distribution among plant organs. Crude extracts of fungal isolates were tested for antifungal and insecticidal biological activities. A total of 16 extracts (41%) showed antifungal properties;while just the extract of M. indicus exhibited larvicidal activity against A. aegypti. These results suggest that the symbiosis between the endophytic fungal community and micropropagated clones of E. purpurea was re-established after acclimatization to soil and the endophytic fungi produced compounds against phytopathogenic fungi.

Salvia ceratophylla L. from South of Jordan: new insights on chemical composition and biological activities

In Jordan,Salvia ceratophylla L.is traditionally used in the treatment of cancer,microbial infections,and urinary disorders.This study aimed:(1)to chemically characterize S.ceratophylla essential oil(EO)from South Jordan,by gas chromatography(GC)and gas chromatography-mass spectrometry(GC-MS);and(2)to evaluate in vitro the cytotoxic,anti-inflammatory,and antiprotozoal activities of the EO,it’s predominant components,and the hexane(A),ethyl acetate(B),methanol(C)and crude-methanol extracts(D).The analysis revealed that the EO has 71 compounds,with linalool(54.8%)as main constitu-ent.Only the hexane extract(A)showed some cytotoxic activity against SK-MEL,KB,BT-549,SK-OV-3,LLC-PK1 and VERO cells lines with IC50 between 60 and>100μg/mL.The EO inhibited NO production(IC5090μg/mL)and NF-κB activity(IC5038μg/mL).The extracts A,B,and D inhibited NO production and NF-κB activity with IC50 between 32 and 150μg/mL.Linalool considerably inhibited NO production(IC5018μg/mL).The extracts tested did not exhibit antileish-manial activity.Regarding antitrypanosomal activity,the EO exhibited significant results with IC502.65μg/mL.In conclu-sion,Jordan S.ceratophylla EO represents a rich source of linalool and bears a promising therapeutic potential for further antitrypanosomal drug development.

Toxicity Evaluation of Acrylamide on the Early Life Stages of the Zebrafish Embryos (<i>Danio rerio</i>)

Acrylamide is a chemical used mainly in industrial applications and the treatment of drinking and wastewater, making it easy to enter aquatic ecosystems. There are few studies known about the toxicity of acrylamide to aquatic organisms which have shown evidence of a number of histopathological effects. To assess the effects of acrylamide to freshwater fish, Zebrafish (Danio rerio) embryos were exposed to serial concentrations of acrylamide (0, 100, 300, and 500 mg/L) to investigate the acute toxicity effects on teleost embryogenesis. Embryos less than 24 hrs old were exposed under static non-renewal conditions for ten days or until hatching. The toxic endpoints evaluated include: egg/embryo viability, hatchability, and morphological/developmental anomalies during organogenesis. The acute toxicity test resulted in a 48 h-LC50 of 585 mg/L for egg viability. Exposure of embryos significantly reduced hatchability and larval survival, in a concentration dependent manner. Dimethyl sulfoxide (DMSO) was used as a solvent carrier to permeate the uptake of acrylamide through the chorion membrane. No significant damages or complications were observed in embryos exposed to DMSO. At 500 mg/L, the highest test concentration, the survival of embryos was greatly reduced within 24 hrs of exposure. The lower test, 100 mg/L, produced a significant number of developmental anomalies to the Zebrafish that included dorsal tail flexure, severe pericardial edema, facial and cranial defects and decreased heartrate (40 bpm). Premature hatching of embryos and developmental arrest was observed in all concentrations. The severity of these anomalies was concentration-dependent and resulted in low survival rate and high frequency of malformations. These results indicate that acrylamide is teratogenic and provide support for sub-lethal toxicity testing using Zebrafish embryos.

Characterization of the Allelopathic Potential of Sugarcane Leaves and Roots

Sugarcane cultivars that are currently planted are the result of genetic improvement focused on increased crop yield. However, this selection and genetic alteration reduced the competitive potential of sugarcane, as well as its allelopathic capabilities. Many members of the Poaceae family are highly allelopathic. Thus, the objective of this study was to characterize the allelopathic potential of two sugarcane cultivars (CTC 2 and IAC 91109) by bioassay-guided fractionation, isolation, and identification of significant phytotoxins, including those that are lipophilic. For both leaves and roots, alpha-linolenic and linoleic acid were found to be the most phytotoxic compounds found with this approach. Both compounds were phytotoxic when applied in soil and caused light-independent cellular leakage of treated cucumber cotyledon discs. We conclude that some of the phytotoxic effects of sugarcane residues in soil are due to the combined action of alpha-linolenic and linoleic acid.

In Vitro Propagation and Conservation of Zeyheria montana Mart:An Endangered Medicinal Plant

Roots of Zeyheriamontana, a species native to the savanna (Cerrado) region of central Brazil, produce lapachol, a naphthoquinone with anticancer activity. Lapachol is also the precursor of β-lapachone, a novel drug candidate for preventive and adjuvant cancer therapies. The leaves of Z. montana are a renewable source of ursolic acid and oleanoic acid, compounds known for their anticancer, antioxidant and antimicrobial properties. The potential prophylactic use of β-lapachone, as well as the medicinal properties of ursolic acid, highlights the importance of this study on Z.montana’s germplasm conservation. Multiple shoots were induced on Woody Plant media with supplemented 0.1 mg·L-1 of thidiazuron (TDZ). Rooting was promoted on half strength WP (Woody Plant media containing 1.0 mg·L-1 of Indolbutiric acid-IBA). Plantlet acclimatization to ex-vitro condition was done at a 70% success rate using different substrates. It was possible to store Z.montana’s elite germplasm using in vitro cultures of media containing 2% sucrose plus 4% sorbitol for six months without subcultures.

Comparative analysis of chemical profiles of Radix Astragali between ultrafine granular powder and sliced traditional material

Radix Astragali,one of the most popular herbs in traditional Chinese medicine(TCM),is used to strengthen the immune system,protect liver function,fight bacteria and viruses,and treat diabetes,heart failure and seasonal allergies.In recent years,a new form of Radix Astragali material processed by cell wall disrupting technology,namely ultrafine granular powder(UGP)has been introduced into the market.In order to determine chemical consistency and homogeneity of the UGP material prepared from sliced traditional materials(TM)of Radix Astragali,multiple batches of the UGP and TM samples derived from Astragalus membranaceus var.mongholicus were analyzed by UHPLC/DAD-MS using isoflavones and triterpenoid glycosides as marker compounds.The results demonstrated that the chemical profiles of UGP was identical or similar to that of TM,but UGP was highly homogeneous in terms of marker compound contents as assessed,e.g.,by the relative standard deviation values of the nine marker compounds in the range of 8.55%−43.80%for TM2 compared against 1.70%−8.38%for UGP2.Macromolecular component preparation and 1H NMR analyses indicated that TM4 and its corresponding UGP4 produced similar polysaccharides,but the later had approximately two-fold dissolution rate of the polysaccharides when compared to the former(yield 7.22±0.35%vs 3.39±0.20%).This study confirms that UGP of Radix Astragali is chemically consistent and homogenous,supporting its use as a promising material in TCM prescriptions.

新型含嘧啶环结构的1,3,4-噻二唑硫醚类化合物的合成及生物活性

为寻找新型杂环活性化合物,通过活性亚结构拼接方法,以硫脲和乙酰丙酮为起始原料合成4,6-二甲基嘧啶-2-硫醇,随后经醚化、肼化、环化和苄基化反应,采用微波促进方法合成了15个新型含嘧啶环结构的1,3,4-噻二唑硫醚类化合物.利用~1H NMR,^(13)C NMR,IR,ESI-MS及元素分析对其结构进行了表征确认.生物活性测试结果表明,在50μg/m L浓度下,部分目标化合物对尖孢炭疽菌、枸杞炭疽菌和草莓炭疽菌具有较好的杀菌活性,其中2-(3-氟苄硫基)-5-(4,6-二甲基嘧啶-2-甲硫基)-1,3,4-噻二唑(7i)对尖孢炭疽菌和草莓炭疽菌的抑制率分别为79.84%和73.46%;若干化合物还表现出良好的抗杜氏利什曼原虫活性,其中2-(2-氟苄硫基)-5-(4,6-二甲基嘧啶-2-甲硫基)-1,3,4-噻二唑(7h)和2-(4-氟苄硫基)-5-(4,6-二甲基嘧啶-2-甲硫基)-1,3,4-噻二唑(7j)的IC50分别为21.3和23.6μg/m L.