Cynanchum atratum Bunge（C. atratum） and Cynanchum versicolor Bunge（C. versicolor） are two related species that have been used as ‘‘Baiwei”（Cynanchi Atrati Radix Et Rhizoma） in traditional medicine in China and other Asian countries for a long time. However, to date, no comprehensive review of C. atratum and C. versicolor has been published. This review provides a comprehensive summary on the botany, phytochemistry, traditional uses and pharmacology of Baiwei; The authors focus especially on the revision of errors in previous articles and reviews, updating information and providing a comparison of C. atratum and C. versicolor. Furthermore, current research reveals significant disparities in the chemical composition and pharmacological effects between C. atratum and C. versicolor. Up to November 2023, 178 compounds have been isolated from C. atratum and C. versicolor, including C 21 steroids, acetophenones,alkaloids and volatile oils. These compounds and extracts have been proven to exhibit significant pharmacological activities, including anti-inflammatory, anti-tumor, anti-virus, anti-fungal, memoryenhancing and anti-pyretic action, immune modulatory effects, reducing blood lipid, inhibition of melanin production, and anti-parasitic effects. Therefore, this review presents new insights into these two herbs used as ‘‘Baiwei” and further study is warranted to enhance their clinical application.

Due to clinical demands, there remains a need for new triazole antifungal compounds to broaden the antifungal spectrum and enhance therapeutic efficacy. In this paper, we have developed an effective method for obtaining triazole compounds with 1,2,3-triazole groups introduced into their side chains via click chemistry, targeting the active site of cytochrome P450 14 alpha-demethylase (CYP51). In vitro antifungal activity tests of the title compounds against three human pathogenic fungi demonstrated that this class of compounds exhibited good antifungal activity. Notably, compound 2d exhibits superior antifungal activity compared to fluconazole against Candida albicans SC5314 (with the MIC value of <= 0.125 mu g/mL) and Cryptococcus neoformans 32609 (with the MIC value of 2 mu g/mL), meriting further investigation. Molecular docking results indicated that the introduced 1,2,3-triazole rings in the side chains formed pi-pi stacking interactions with Tyr118 of CYP51, along with additional hydrogen bonds. This paper provides a method for rapidly modifying the side chains of triazole antifungal drugs in the future to obtain compounds with further enhanced activity.

Life-threatening invasive fungal infections pose a serious threat to human health. A series of novel triazole derivatives bearing a pyrazole-methoxyl moiety were designed and synthesized in an effort to obtain antifungals with potent, broad-spectrum activity that are less susceptible to resistance. Most of these compounds exhibited moderate to excellent in vitro antifungal activities against Candida albicans SC5314 and 10,231, Cryptococcus neoformans 32,609, Candida glabrata 537 and Candida parapsilosis 22,019 with minimum inhibitory concentration (MIC) values of ≤0.125 μg/mL to 0.5 μg/mL. Use of recombinant Saccharomyces cerevisiae strains showed compounds 7 and 10 overcame the overexpression and resistant-related mutations in ERG11 of S. cerevisae and several pathogenic Candida spp. Despite being substrates of the C. albicans and Candida auris Cdr1 drug efflux pumps, compounds 7 and 10 showed moderate potency against five fluconazole (FCZ)-resistant fungi with MIC values from 2.0 μg/mL to 16.0 μg/mL. Growth kinetics confirmed compounds 7 and 10 had much stronger fungistatic activity than FCZ. For C. albicans, compounds 7 and 10 inhibited the yeast-to-hyphae transition, biofilm formation and destroyed mature biofilm more effectively than FCZ. Preliminary mechanism of action studies showed compounds 7 and 10 blocked the ergosterol biosynthesis pathway at Erg11, ultimately leading to cell membrane disruption. Further investigation of these novel triazole derivatives is also warranted by their predicted ADMET properties and low cytotoxicity.

Invasive fungal infections pose a serious threat to public health and are associated with high mortality and incidence rates. The development of novel antifungal agents is urgently needed. Based on hit-to-lead optimization, a series of 2,4,6-trisubstituted triazine hydrazone compounds were designed, synthesized, and biological evaluation was performed, leading to the identification of compound 28 with excellent in vitro synergy (FICI range: 0.094-0.38) and improved monotherapy potency against fluconazole-resistant Candida albicans and Candida auris (MIC range: 1.0-16.0 mu g/mL). Moreover, 28 exhibited broad-spectrum antifungal activity against multiple pathogenic strains. Furthermore, 28 could inhibit hyphal and biofilm formation, which may be related to its ability to disrupt the fungal cell wall. Additionally, 28 significantly reduced the CFU in a mouse model of disseminated infection with candidiasis at a dose of 10 mg/kg. Overall, the triazine-based hydrazone compound 28 with low cytotoxicity, hemolysis, and favorable ADME/T characteristics represents a promising lead to further investigation.

Objective: Qu Du Qiang Fei 1 Hao Fang（QDQF1） is a novel Chinese herbal medicine formula used to treat coronavirus disease 2019（COVID-19）. However, the pharmacological mechanisms of action of QDQF1 remain unclear. The objective of this study was to identify the effective ingredients and biological targets of QDQF1 for COVID-19 treatment. Materials and Methods: The effective ingredients and mechanisms of action of QDQF1 were analyzed by using network pharmacology methods, which included an analysis of the effective ingredients and corresponding targets, COVID-19-related target acquisition, compound-target network analyses, protein-protein interaction network analysis, Kyoto Encyclopedia of Genes and Genomes（KEGG） and Gene Ontology（GO） enrichment analyses, and molecular docking studies. Results: In total, 288 effective QDQF1 ingredients were identified. We identified 51 core targets from the 148 targets through an overlap between putative QDQF1 targets and COVID-19-related targets. Six key components, including formononetin, kaempferol, luteolin, naringenin, quercetin, and wogonin were identified through component-target network analyses. GO functional enrichment analysis of the core targets revealed 1296 items, while KEGG pathway enrichment analysis identified 148 signaling pathways. Nine central targets（CCL2, CXCL8, IL1B, IL6, MAPK1, MAPK3, MAPK8, STAT3, and TNF） related to the COVID-19 pathway were identified in the KEGG pathway enrichment analysis. Furthermore, molecular docking analysis suggested that the docking scores of the six key components to the nine central targets were better than those to remdesivir. Conclusions: QDQF1 may regulate multiple immune-and inflammation-related targets to inhibit the progression of severe acute respiratory syndrome coronavirus 2, and thus, may be suitable for the treatment of COVID-19.

Natural product-based antiviral candidates have received significant attention. However, there is a lack of sufficient research in the field of antivirals to effectively combat patterns of drug resistance. Baicalein and its glucuronide derivative baicalin are two main components extracted from Scutellaria baicalensis Georgi. They have proven to be effective against a broad range of viruses by directly killing virus particles, protecting infected cells, and targeting viral antigens on their surface, among other mechanisms. As natural products, they both possess the advantage of lower toxicity, enhanced therapeutic efficacy, and even antagonistic effects against drug-resistant viral strains. Baicalein and baicalin exhibit promising potential as potent pharmacophore scaffolds, demonstrating their antiviral properties. However, to date, no review on the antiviral effects of baicalein and baicalin has been published. This review summarizes the recent research progress on antiviral effects of baicalein and baicalin against various types of viruses both in vitro and in vivo with a focus on the dosages and underlying mechanisms. The aim is to provide a basis for the rational development and utilization of baicalein and baicalin, as well as to promote antiviral drug research.

Organic chemistry is a fundamental course for undergraduate students majoring in clinical disciplines at our university,playing a crucial"bridge"role in their subsequent professional courses.However,organic chemistry is known for its abstract theoretical concepts and numerous knowledge points,making it challenging for students to comprehend and master.In response to the teaching issues encountered in traditional classroom settings,this paper adopts the innovative O-PIRTAS flipped classroom model,integrating the characteristics of organic chemistry education.Taking the specific topic of carboxylic acids as an example,the classroom teaching is restructured with the aim of exploring the application of this model in organic chemistry courses and subsequently improving teaching effectiveness.

In recent years, some large public hospitals in China had successively opened scientific research outpatients to provide consulting services for clinical research, but there were generally problems such as insufficient audience and single role of expert teams. In July 2021, Shanghai Clinical Research Center established a multidisciplinary scientific research outpatient for the entire clinical research cycle, providing medical staffs with such services as clinical research design and project application, paper revision and achievement transformation. It also provided clerkship for medical students on campus to cultivate their standardized clinical research thinking. As of July 2022, the outpatient had provided research consulting services 16 times, teaching 8 class hours to medical students, and collaborated to solve multi-dimensional clinical research practical problems throughout the entire cycle, such as clinical trial design, project application, and paper publication. Good results had been achieved by this outpatient to provide reference for promoting the development of scientific research outpatients in China and improving the clinical research level of hospitals.

Background The synergistic effect of dihydromyricetin (DHM) and fluconazole (FLC) can improve the killing effect of FLC-resistant Candida albicans in vitro and in vivo. However, it is not clear whether DHM affects the pharmacokinetic characteristics of FLC. Methods In this study, 12 Sprague–Dawley (SD) rats were randomly divided into two groups as follows: (1) an FLC group in which rats were administered FLC only (42 mg/kg orally); (2) an FLC with the combined administration of DHM group, in which rats received an equivalent FLC dose immediately following the administration of DHM (100 mg/kg). Blood samples were collected from the ocular choroid vein of rats and converted into plasma. The concentrations of FLC in the rat plasma were then determined by high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS), and the related pharmacokinetic parameters were analysed. The initial mobile phase included 0.1% acetonitrile and water with gradient elution. Multiple reaction monitoring modes of m/z 307.2→220.1 for FLC, and m/z 237.1→194.2 for carbamazepine, were utilised to conduct quantitative analysis. Results The calibration curve of FLC in rat plasma demonstrated good linearity in the range of 0.1–30 μg/mL (r > 0.99), and the lower limit of quantification was 0.1 μg/mL. Moreover, the intra- and inter-day precision relative standard deviation of FLC was less than 9.09% and 6.51%, respectively. There were no significant differences in the pharmacokinetic parameters between the two groups. Conclusion The results showed that DHM administration did not significantly alter FLC pharmacokinetics in SD rat plasma.

BOPPPS教学模式是一种逻辑清晰、教学节奏紧凑的教学模型,按照模块设置顺序,包含了导入、目标、前测、参与式学习、后测和总结六大部分.针对临床专业有机化学课时数少、知识点零碎、理论抽象等特点,教学团队运用BOPPPS教学模式,以"羧酸"章节授课为例,探讨该模式在有机化学课程中的应用.

Chikungunya fever is an acute infectious disease caused by Chikungunya virus (CHIKV) and transmitted by Aedes mosquito. It is characterized by fever, rash and arthralgia with no effective drugs. Lomerizine (Lom) is a new generation calcium antagonist, which is mainly used in the treatment of migraine. Certain antiviral function of Lom was shown by some research. In our study, a series of new derivatives of Lom were designed and synthesized, and their in-vitro anti-CHIKV activity was tested. The results showed that Lom and its derivatives had potent anti-CHIKV activity and low cytotoxicity. Among them, compounds B1 and B7 showed most potent antiviral activity. Besides, structure-activity relationships, in-silico ADMET properties were also analyzed. Molecular docking study was performed to rationalize the SAR and analyze the possible binding modes between B1 and amino acid residues in the active site of nsP3 protein to enhance the understanding of their action as antiviral agents. These finding provides research basis for the design and synthesis of effective anti-CHIKV drugs with Lom as the lead compound.

Previous work led to the rational design, synthesis and testing of novel antifungal triazole analogues bearing alkynyl-methoxyl side chains. Tests of in vitro antifungal activity showed Candida albicans SC5314 and Candida glabrata 537 gave MIC values of ≤0.125 μg/mL for most of the compounds. Among these, compounds 16, 18, and 29 displayed broad-spectrum antifungal activity against seven human pathogenic fungal species, two fluconazole-resistant C. albicans isolates and two multi-drug resistant Candida auris isolates. Moreover, 0.5 μg/mL of 16, 18, and 29 was more effective than 2 μg/mL of fluconazole at inhibiting fungal growth of the strains tested. The most active compound (16) completely inhibited the growth of C. albicans SC5314 at 16 μg/mL for 24 h, affected biofilm formation and destroyed the mature biofilm at 64 μg/mL. Several Saccharomyces cerevisiae strains, overexpressing recombinant Cyp51s or drug efflux pumps, indicated 16, 18, and 29 targeted Cyp51 without being significantly affected by a common active site mutation, but were susceptible to target overexpression and efflux by both MFS and ABC transporters. GC-MS analysis demonstrated that 16, 18, and 29 interfered with the C. albicans ergosterol biosynthesis pathway by inhibition at Cyp51. Molecular docking studies elucidated the binding modes of 18 with Cyp51. The compounds showed low cytotoxicity, low hemolytic activity and favorable ADMT properties. Importantly, compound 16 showed potent in vivo antifungal efficacy in the G. mellonella infection model. Taken together, this study presents more effective, broad-spectrum, low toxicity triazole analogues that can contribute to the development of novel antifungal agents and help overcome antifungal resistance.

A series of novel triazole derivatives containing aryl-propanamide side chains was designed and synthesised. In vitro antifungal activity studies demonstrated that most of the compounds inhibited the growth of six human pathogenic fungi. In particular, parts of phenyl-propionamide-containing compounds had excellent, broad-spectrum antifungal activity against Candida albicans SC5314, Cryptococcus neoformans 22-21, Candida glabrata 537 and Candida parapsilosis 22-20 with MIC values in the range of & LE;0.125 & mu;g/mL-4.0 & mu;g/mL. In addition, compounds A1, A2, A6, A12 and A15 showed inhibitory activities against fluconazole-resistant Candida albicans and Candida auris. Preliminary structure-activity relationships (SARs) are also summarised. Moreover, GC-MS analysis demonstrated that A1, A3, and A9 interfered with the C. albicans ergosterol biosynthesis pathway by inhibiting Cyp51. Molecular docking studies elucidated the binding modes of A3 and A9 with Cyp51. These compounds with low haemolytic activity and favourable ADME/T properties are promising for the development of novel antifungal agents.

Background: Invasive fungal infections (IFIs) are primarily caused by Candida spp., Cryptococcus neoformans, Aspergillus spp., Mucor spp., Sporothrix spp., and Pneumocystis spp., which attack human organs with a strong pathogenicity and exhibit drug resistance against com-monly used chemical drugs. Therefore, the search for alternative drugs with high efficacy, low re-sistance rates, few side effects, and synergistic antifungal effects remains a major challenge. The characteristics of natural products with structural and bioactive diversity, lower drug resistance, and rich resources make them a major focus of the development of antifungal drugs. Objective: Objectives: This review attempts to summarize the origin, structure, and antifungal activity of natural products and their derivatives with MIC ≤ 20 μg/mL or 100 μM, focusing on their MoA and SAR. Methods: All pertinent literature databases were searched. The search keywords were antifungal or antifungals, terpenoids, steroidal saponins, alkaloid, phenols, lignans, flavonoids, quinones, macro-lide, peptide, tetramic acid glycoside, polyene, polyketide, bithiazole, natural product, and deriva-tives. All the related literature (covering the past 20 years, 2001-2022) was evaluated. Results: In total, 340 natural products and 34 synthesized derivatives with antifungal activity from 301 studies were included in this review. These compounds were derived from terrestrial plants, ocean life, and microorganisms and exhibited in vitro and in vivo potent antifungal activity alone or in combination. The MoA and SARs of reported compounds were summarized whenever applicable. Conclusion: In this review, we attempted to review the available literature on natural antifungal products and their derivatives. Most of the studied compounds showed potent activity against Can-dida species, Aspergillus species, or Cryptococcus species. Some of the studied compounds also demonstrated the ability to impair the cell membrane and cell wall, inhibit hypha and biofilms, and cause mitochondrial dysfunction. Although the MoAs of these compounds are not well understood yet, they can be used as lead components for the development of new, effective, and safe antifungal agents through their novel mechanisms.

Baicalein (BE), the major component of Scutellaria Baicalensis, exhibited potently antifungal activity against drug-resistant Candida albicans, and strong inhibition on biofilm formation. Therefore, a series of baicalein-core derivatives were designed and synthesized to find more potent compounds and investigate structure–activity relationship (SAR) and mode of action (MoA). Results demonstrate that A4 and B5 exert a more potent antifungal effect (MIC80 = 0.125 μg/mL) than BE (MIC80 = 4 μg/mL) when used in combination with fluconazole (FLC), while the MIC80 of FLC dropped from 128 μg/mL to 1 μg/mL. SAR analysis indicates that the presence of 5-OH is crucial for synergistic antifungal activities, while o-dihydroxyls and vic-trihydroxyls are an essential pharmacophore, whether they are located on the A ring or the B ring of flavonoids. The MoA demonstrated that these compounds exhibited potent antifungal effects by inhibiting hypha formation of C. albicans. However, sterol composition assay and enzymatic assay conducted in vitro indicated minimal impact of these compounds on sterol biosynthesis and Eno1. These findings were further confirmed by the results of the in-silico assay, which assessed the stability of the complexes. Moreover, the inhibition of hypha of this kind of compound could be attributed to their effect on the catalytic subunit of 1,3-β-d-glucan synthase, 1,3-β-d-glucan-UDP glucosyltransferase and glycosyl-phosphatidylinositol protein, rather than inhibiting ergosterol biosynthesis and Eno1 activity by Induced-Fit Docking and Molecular Dynamics Simulations. This study presents potential antifungal agents with synergistic effects that can effectively inhibit hypha formation. It also provides new insights into the MoA.

目的 利用数据挖掘的方法探究历代医家治疗肥胖型多囊卵巢综合征(PCOS)的处方规律,归纳核心处方与药物,并利用网络药理学探讨核心处方的潜在物质基础与作用机制,为中医药治疗肥胖型PCOS提供参考.方法 以《中华医典》为资料来源,利用Excel 2018 建立肥胖型PCOS处方数据库,借助SPSS Modeler 18 及Gephi 0.9.7 软件对符合肥胖型PCOS表现的处方药物进行关联分析.利用中药系统药理学数据库与分析平台(TCMSP)获取核心药对的成分及靶基因,利用人类基因数据库(GeneCard)和在线人类孟德尔遗传数据库(OMIM)获取肥胖型PCOS靶基因,进一步获取核心药物靶基因与肥胖型PCOS靶基因的交集基因.利用Cytoscape 3.7.1 软件构建核心药物活性成分-交集基因网络,并利用可视化和集成发现数据库(DAVID)进行组织富集分析.结果 共得到符合肥胖型PCOS的处方 47 首,涉及中药 98 味,使用频次≥5 的中药为茯苓、半夏、甘草、陈皮、川芎、香附、白术、当归、苍术、南星、人参、滑石、枳壳、白芍、黄连、地黄、橘红、砂仁;有强关联的核心药对组合为半夏、陈皮、茯苓、甘草(二陈汤).利用TCMSP 数据库获得二陈汤的药物成分 125 个、靶基因 218 个,利用GeneCard数据库及OMIM获得肥胖型PCOS靶基因 2 962 个,获得肥胖型PCOS靶基因与核心药物靶基因的交集基因 149个.网络药理学分析显示,度值较高的药物活性成分有槲皮素、山奈酚、芒柄花素等,度值较高的靶基因包括前列腺素内过氧化物合酶 2、雌激素受体 1、雄激素受体等.组织富集分析结果显示,交集靶基因主要富集在胎盘、肝脏、肺、上皮等组织.结论 数据挖掘结果提示,历代医家治疗肥胖型PCOS时以益气健脾、燥湿化痰为主要原则,同时佐以养血调经的药物.网络药理学结果验证了古文献分析结果,提示黄酮类化合物可能通过调控激素受体改善肥胖型PCOS.

In order to develop new triazole derivatives, we optimized the lead compound a6 by structural modifications to obtain a series of (2R,3R)-3-((1-substituted-1H-1,2,3-triazol-4-yl) methoxy)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl) butan-2-ol, compounds 5-36. Most of the target compounds exhibited excellent in vitro antifungal activity against Candida albicans 10231 and Candida glabrata 537 with MIC ≤ 0.125 µg/mL. Of particular note, compounds 6, 22, 28, 30 and 36 were highly active against Candida neoformans 32609 with MIC ≤ 0.125 µg/mL and showed broad-spectrum antifungal activity including against fluconazole-resistant Candida auris 891. In addition, compounds 6 and 22 demonstrated inhibitory effects on filamentation in the azole-resistant C. albicans isolate. Moreover, compounds 6 and 22 were minimally toxic to HUVECs and possessed weak inhibitory effects on the human CYP3A4 and CYP2D6. SARs and docking study further indicated that ortho-substituted groups in the terminal phenyl ring can promote the compounds to improve their antifungal activity.

目的 探究二陈汤治疗肥胖型多囊卵巢综合征和肥胖型不孕的潜在机制,为"异病同治"提供理论依据.方法 利用TCMSP数据库获取二陈汤的活性成分与靶点,利用Genecard数据库获取肥胖型多囊卵巢综合征和肥胖型不孕的靶点.利用Cytoscape 3.7.1构建活性成分靶点网络,利用STRING获取蛋白互作网络与核心靶点.利用Cytoscape 3.7.1与线上软件进行GO与KEGG富集分析.结果 获得二陈汤成分125个,靶基因218个;肥胖型不孕靶基因2783个,肥胖型多囊卵巢综合征靶基因2962个.二陈汤治疗肥胖型不孕和肥胖型多囊卵巢综合征的共有靶基因117个,体现了"异病同治"的原则;潜在的活性成分包括槲皮素、山奈酚、柚皮素、黄芩苷和刺芒柄花素.蛋白互作网络示STAT3、JUN、AKT1、MAPK3、MAPK1、MAPK14、IL-6和FOS为"异病同治"的核心靶点.分子对接结果显示,槲皮素、山奈酚等成分与JUN具有较好的结合能力.GO与KEGG富集分析显示,AGE-RAGE信号通路、IL-17信号通路、内分泌抵抗可能是二陈汤"异病同治"的关键通路.结论 二陈汤"异病同治"肥胖型多囊卵巢综合征和肥胖型不孕涉及相同靶点以及通路,可为以后的实验研究提供参考.

目的 通过癌症基因组图谱(TCGA)数据库挖掘与乳腺癌预后相关的铁死亡基因,构建乳腺癌预后模型.方法 下载TCGA数据库中转录组与临床数据,获取与预后相关的在乳腺癌组织与癌旁正常组织中存在差异表达的铁死亡基因,利用最小绝对收缩和选择算子(LASSO)回归法构建风险评分模型.将TCGA数据库中获取的患者信息作为模型测试集数据,通过ROC曲线评估预后模型的效能,通过单因素与多因素Cox回归分析评价差异表达的铁死亡基因和风险评分能否作为预后因子.利用国际肿瘤基因组协作组(ICGC)数据库与基因表达汇编(GEO)数据库数据作为验证集对该模型进行验证.结果 共筛选出51个在乳腺癌组织与癌旁正常组织中存在差异表达的铁死亡基因,单因素Cox回归分析表明11个差异表达的铁死亡基因与乳腺癌预后相关.利用这11个基因构建乳腺癌预后风险评分模型:风险评分=ALOX15×0.11+CHAC1×0.07+CISD1×0.15+CS×0.24+GCLC×0.04+GPX4×(-0.07)+NCOA4×0.17+EMC2×0.30+G6PD×0.19+ACSF2×(-0.04)+SQLE×0.12,ROC曲线分析表明该模型在测试集中预测乳腺癌患者术后2、4、6年生存率的AUC分别为0.678、0.680、0.612,多因素Cox回归分析结果显示预后模型风险评分可作为独立预后因子(HR=3.104,P<0.001).根据预后模型风险评分是否≥4.277将患者分为高风险组和低风险组,在测试集与验证集中高风险组患者的生存率均低于低风险组患者(P均<0.001).结论 基于铁死亡基因的乳腺癌预后模型具有较好的预测效能,该模型中的铁死亡基因为乳腺癌靶向治疗提供了新的靶点.

The clinical prevalence of antifungal drug resistance has been increasing over recent years, resulting in the failure of treatments. In an attempt to overcome this critical problem, we sought novel synergistic enhancers to restore the effectiveness of fluconazole against resistant Candida albicans. Based on the structural optimization of hit compound 8 from our in-house library, a series of novel 1,3,5-triazines derivatives was designed, synthesized, and biologically evaluated for synergistic activity in combination with fluconazole. Among them, compounds 10a–o, which contain thiosemicarbazides side chains, exhibited excellent in vitro synergistic antifungal potency (MIC80 = 0.125–2.0 μg/mL, FICI range from 0.127 to 0.25). Interestingly, compound 10l exhibited moderate C. albicans activity as monotherapy with an MIC80 value of 4.0 μg/mL, and also on several Cryptococcus strains (MIC80 ranging from ≤ 0.125–0.5 μg/mL) and C. glabrata (MIC80 ≤ 0.125 μg/mL). These effects were fungal-selective, with much lower levels of cytotoxicity towards human umbilical vein endothelial cells. Here, we report a series of thiosemicarbazides containing 1,3,5-triazines derivatives as potent synergists with fluconazole, and have preliminarily validated compound 10l as a promising antifungal lead for further investigation.