1. Tingting Wang, Yunping Feng, Jian Huang, Sitong Wu, Kun Hu, Jiabin Wu, C. Benjamin Naman, Hong Wang, Wenhan Lin, Shan He*.  Pestanoid A, a Rearranged Pimarane Diterpenoid Osteoclastogenesis Inhibitor from a Marine Mesophotic Zone Chalinidae Sponge-Associated Fungus, Pestalotiopsis sp. NBUF145. Journal of Natural Products, 2024, 87, 1, 160–165. (https://doi.org/10.1021/acs.jnatprod.3c00892) IF: 5.1

Abstract

One novel rearranged pimarane diterpenoid, pestanoid A (1), and two reported molecules, nodulisporenones A (2) and B (3), were discovered from Pestalotiopsis sp. NBUF145 fungus associated with a 62 m deep mesophotic (“twilight”) zone Chalinidae sponge. The structures of 1–3 were identified by spectrometry, spectroscopy, quantum-chemical calculations, and X-ray crystallography. Compounds 1 and 2 inhibited bone marrow monocyte osteoclastogenesis in vitro with the IC50 values 4.2 ± 0.2 μM and 3.0 ± 0.4 μM, respectively, without observed cytotoxicity. Both 1 and 2 suppressed the receptor activator of NF-kB ligand-induced MAPK and NF-κB signaling by inhibiting the phosphorylation of ERK1/2-JNK1/2-p38 MAPKs and NF-κB nuclear translocation.

2. Zhikun Yang, Disheng Luo, Chen Shao（本科生）, Haoqiang Hu, Xue Yang, Yue Cai, Xiaozhou Mou, Qihao Wu, Hongtao Xu, Xuanrong Sun, Hong Wang*, Wei Hou*. Design, synthesis, and bioactivity evaluation of novel indole-selenide derivatives as P-glycoprotein inhibitors against multi-drug resistance in MCF-7/ADR cell. European Journal of Medicinal Chemistry, 2024, 268:116207.（https://doi.org/10.1016/j.ejmech.2024.116207）IF：6.7

Abstract

The inhibition of P-glycoprotein (P-gp) has emerged as an intriguing strategy for circumventing multidrug resistance (MDR) in anticancer chemotherapy. In this study, we have designed and synthesized 30 indole-selenides as a new class of P-gp inhibitors based on the scaffold hopping strategy. Among them, the preferred compound H27 showed slightly stronger reversal activity (reversal fold: 271.7 vs 261.6) but weaker cytotoxicity (inhibition ratio: 33.7% vs 45.1%) than the third-generation P-gp inhibitor tariquidar on the tested MCF-7/ADR cells. Rh123 accumulation experiments and Western blot analysis demonstrated that H27 displayed excellent MDR reversal activity by dose-dependently inhibiting the efflux function of P-gp rather than its expression. Besides, UIC-2 reactivity shift assay revealed that H27 could bind to P-gp directly and induced a conformation change of P-gp. Moreover, docking study revealed that H27 matched well in the active pockets of P-gp by forming some key H−bonding interactions, arene−H interactions and hydrophobic contacts. These results suggested that H27 is worth to be a starting point for the development of novel Se-containing P-gp inhibitors for clinic use.

3. Chen Wenchao, Chen Li, Chen Junbo, Wu Wentao, Yu Yanlei, Wang Hong*, Richmond Lee*, Tan Choon-Hong*, Ye Xinyi*. Bisguanidinium-catalyzed remote enantioselective desymmetrization with 1,2-acyl shift. Chem Catalysis, 2024, 4(4): 100953. (https://www.sciencedirect.com/science/article/pii/S2667109324000770) IF：10.80

Abstract

In this work, we described a remote desymmetrization reaction in which cesium carboxylate, in the presence of bisguanidinium as catalyst, was added to (cis)-α,α′-dibromocyclohexanone to access 6-oxocyclohex-1-enyl ester via a 1,2-acyl shift in a highly enantioselective fashion. In this process, the carboxylate initiated a nucleophilic attack, and then a keto-enol tautomerism led to a 1,2-acyl shift to the neighboring alcohol. Key intermediates were isolated and determined using single-crystal X-ray crystallography. The remote desymmetrization that includes stepwise SN2 and intramolecular acyl transfer was proposed and was further supported using computational studies. Finally, it was successfully applied to a tropinone derivative, realizing carbonyl chain walking efficiently.

4. Man-Jing Ma#, Wen-Chao Yu#, Huai-Ying Sun, Bing-Cheng Dong, Gang-Ao Hu, Zhen-Yi Zhou, Yi Hua, Buddha Bahadur Basnet, Hong Wang*, Bin Wei*. Genus-specific secondary metabolome in Allokutzneria and Kibdelosporangium. Synthetic and Systems Biotechnology，2024, 9(3):381. (https://doi.org/10.1016/j.synbio.2024.03.015) IF：4.80

Abstract

Rare actinomycete genera are highly recognized as a promising source of structurally diverse and bioactive natural products. Among these genera, Allokutzneria and Kibdelosporangium are two phylogenetically closely related and have been reported to encode some valuable biosynthetic enzymes and secondary metabolites. However, there is currently no relevant systematic research available to outline the linkage of genomic and metabolomics for specific secondary metabolites in these two promising genera. In this study, we first investigated the genus-specific secondary metabolic potential in Allokutzneria and Kibdelosporangium by comparing the diversity and novelty of their secondary metabolite biosynthetic gene clusters (BGCs). The specific secondary metabolites produced by two representative strains of these genera were comprehensively investigated using untargeted metabolomics techniques. The findings unveiled that the majority (95.4%) of the gene cluster families (GCFs) encoded by Allokutzneria and Kibdelosporangium were genus-specific, including NRPS GCFs encoding siderophores. The untargeted metabolomics analysis revealed that the metabolic profiles of two representative strains exhibit extensive specificity, with the culture medium having a big impact on the metabolic profiles. Besides, an MS-cluster featuring a series of hydroxamate-type siderophores was identified from Allokutzneria albata JCM 9917, with two of them, including a novel one (N-deoxy arthrobactin A), being experimentally validated. The present study offers valuable insights for the targeted discovery of genus-specific natural products from microorganisms.

5. Jianwei Chen*, Wei Wang, Xubin Hu, Yujie Yue, Xingyue Lu, Chenjie Wang, Bin Wei, Huawei Zhang, Hong Wang*. Medium-sized peptides from microbial sources with potential for antibacterial drug development. Natural Product Reports. 2024. (https://doi.org/10.1039/D4NP00002A)

Abstract

Covering: 1993 to the end of 2022

As the rapid development of antibiotic resistance shrinks the number of clinically available antibiotics, there is an urgent need for novel options to fill the existing antibiotic pipeline. In recent years, antimicrobial peptides have attracted increased interest due to their impressive broad-spectrum antimicrobial activity and low probability of antibiotic resistance. However, macromolecular antimicrobial peptides of plant and animal origin face obstacles in antibiotic development because of their extremely short elimination half-life and poor chemical stability. Herein, we focus on medium-sized antibacterial peptides (MAPs) of microbial origin with molecular weights below 2000 Da. The low molecular weight is not sufficient to form complex protein conformations and is also associated to a better chemical stability and easier modifications. Microbially-produced peptides are often composed of a variety of non-protein amino acids and terminal modifications, which contribute to improving the elimination half-life of compounds. Therefore, MAPs have great potential for drug discovery and are likely to become key players in the development of next-generation antibiotics. In this review, we provide a detailed exploration of the modes of action demonstrated by 45 MAPs and offer a concise summary of the structure–activity relationships observed in these MAPs.

6. Wenchao Wang, Haonan Xiong, Lei Li, Xialin Hu, Wenya Zhuang, Jiangtao Li, Xuanrong Sun, Yanlei Yu, Yuanquan Yu, Yinghao Guo, Yihang Wang, Ruojiong Wang, Hong Wang, QingYong Li*. Biological impact and therapeutic potential of a novel camptothecin derivative (FLQY2) in pancreatic cancer through inactivation of the PDK1/AKT/mTOR pathway. Bioorganic Chemistry. 2024, 148: 107436. (https://doi.org/10.1016/j.bioorg.2024.107436)

Abstract

7. Yanlei Yu, Yue Song, Yunjie Zhao, Ningning Wang, Bin Wei, Robert J. Linhardt, Jonathan S. Dordick, Fuming Zhang*, Hong Wang*. Quality control, safety assessment and preparation approaches of low molecular weight heparin. Carbohydrate Polymers. 2024. 339: 122216. (https://doi.org/10.1016/j.carbpol.2024.122216)

Abstract

Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin (UFH) due to their predictable pharmacokinetics and subcutaneous bioavailability. LMWHs are produced by various depolymerization methods from UFH, resulting in heterogeneous compounds with similar biochemical and pharmacological properties. However, the delicate supply chain of UFH and potential contamination from animal sources require new manufacturing approaches for LMWHs. Various LMWH preparation methods are emerging, such as chemical synthesis, enzymatic or chemical depolymerization and chemoenzymatic synthesis. To establish the sameness of active ingredients in both innovator and generic LMWH products, the Food and Drug Administration has implemented a stringent scientific method of equivalence based on physicochemical properties, heparin source material and depolymerization techniques, disaccharide composition and oligosaccharide mapping, biological and biochemical properties, and in vivo pharmacodynamic profiles. In this review, we discuss currently available LMWHs, potential manufacturing methods, and recent progress for manufacturing quality control of these LMWHs.

8. Shi-Qiang Wei, Zi-Hao Li, Shuang-Hu Wang, Hua Chen, Xiao-Yu Wang, Yun-Zhou Gu, Ye Zhang, Hong Wang, Tong-Mei Ding, Shu-Yu Zhang*, Yong-Qiang Tu*, Asymmetric Intramolecular Amination Catalyzed with Cp*Ir-SPDO via Nitrene Transfer for Synthesis of Spiro-Quaternary Indolinone. J. Am. Chem. Soc. 2024, 146, 28, 18841–18847. (https://doi.org/10.1021/jacs.4c05560) IF:14.4

Abstract

An asymmetric intramolecular spiro-amination to high steric hindering α-C–H bond of 1,3-dicarbonyl via nitrene transfer using inactive aryl azides has been carried out by developing a novel Cp*Ir(III)-SPDO (spiro-pyrrolidine oxazoline) catalyst, thereby enabling the first successful construction of structurally rigid spiro-quaternary indolinone cores with moderate to high yields and excellent enantioselectivities. DFT computations support the presence of double bridging H–F bonds between [SbF6]− and both the ligand and substrate, which favors the plane-differentiation of the enol π-bond for nitrenoid attacking. These findings open up numerous opportunities for the development of new asymmetric nitrene transfer systems.

9. Keren Xu, Leyi Ying, Titi Ying, Qihao Wu, Lin Du, Yanlei Yu, Youmin Ying, Bin Wei*, Hong Wang*, Zhikun Yang*. Design, synthesis, and biological evaluation of (thio)urea derivatives as potent Escherichia coli β-glucuronidase inhibitors. Journal of Enzyme Inhibition and Medicinal Chemistry. 2024, 39(1):2387415. (DOI - 10.1080/14756366.2024.2387415). IF:5.6

Abstract

EcGUS has drawn considerable attention for its role as a target in alleviating serious GIAEs. In this study, a series of 72 (thio)urea derivatives were designed, synthesized, and biologically assayed. The bioassay results revealed that E-9 (IC50 = 2.68 μM) exhibited a promising inhibitory effect on EcGUS, surpassing EcGUS inhibitor D-saccharic acid-1,4-lactone (DSL, IC50 = 45.8 μM). Additionally, the inhibitory kinetic study indicated that E-9 (Ki = 1.64 μM) acted as an uncompetitive inhibitor against EcGUS. The structure-activity relationship revealed that introducing an electron-withdrawing group into the benzene ring at the para-position is beneficial for enhancing inhibitory activity against EcGUS. Furthermore, molecular docking analysis indicated that E-9 has a strong affinity to EcGUS by forming interactions with residues Asp 163, Tyr 472, and Glu 504. Overall, these results suggested that E-9 could be a potent EcGUS inhibitor, providing valuable insights and guidelines for the development of future inhibitors targeting EcGUS.

10. Jiahao Wang, Xingyue Lu, Chenjie Wang, Yujie Yue, Bin Wei, Huawei Zhang , Hong Wang* and Jianwei Chen*. Research progress on the combination of quorum-sensing inhibitors and antibiotics against bacterial resistance. Molecules. 2024, 29, 1674.

Abstract

Bacterial virulence factors and biofilm development can be controlled by the quorum sensing (QS) system, which is also intimately linked to antibiotic resistance in bacteria. In previous studies, many researchers found that quorum-sensing inhibitors (QSIs) can affect the development of bacterial biofilms and prevent the synthesis of many virulence factors. However, QSIs alone have a limited ability to suppress bacteria. Fortunately, when QSIs are combined with antibiotics, they have a better therapeutic effect, and it has even been demonstrated that the two together have a synergistic antibacterial effect, which not only ensures bactericidal efficiency but also avoids the resistance caused by excessive use of antibiotics. In addition, some progress has been made through in vivo studies on the combination of QSIs and antibiotics. This article mainly expounds on the specific effect of QSIs combined with antibiotics on bacteria and the combined antibacterial mechanism of some QSIs and antibiotics. These studies will provide new strategies and means for the clinical treatment of bacterial infections in the future.

11. Gang-Ao Hu#, Yue Song#,  Shi-Yi Liu, Wen-Chao Yu, Yan-Lei Yu, Hong Wang*, Bin Wei*. Exploring the diversity and specificity ofsecondary biosynthetic potential in Rhodococcus. Marine Drugs (2024), 22, 409. (https://doi.org/10.3390/md22090409)

Abstract

The actinomycete genus Rhodococcus is known for its diverse biosynthetic enzymes, with potential in pollutant degradation, chemical biocatalysis, and natural product exploration. Comparative genomics have analyzed the distribution patterns of non-ribosomal peptide synthetases (NRPSs) in Rhodococcus. The diversity and specificity of its secondary metabolism offer valuable insights for exploring natural products, yet remain understudied. In the present study, we analyzed the distribution patterns of biosynthetic gene clusters (BGCs) in the most comprehensive Rhodococcus genome data to date. The results show that 86.5% of the gene cluster families (GCFs) are only distributed in a specific phylogenomic-clade of Rhodococcus, with the most predominant types of gene clusters being NRPS and ribosomally synthesized and post-translationally modified peptides (RiPPs). In-depth mining of RiPP gene clusters revealed that Rhodococcus encodes many clade-specific novel RiPPs, with thirteen core peptides showing antibacterial potential. High-throughput elicitor screening (HiTES) and non-targeted metabolomics revealed that a marine-derived Rhodococcus strain produces a large number of new aurachin-like compounds when exposed to specific elicitors. The present study highlights the diversity and specificity of secondary biosynthetic potential in Rhodococcus, and provides valuable information for the targeted exploration of novel natural products from Rhodococcus, especially for phylogenomic-clade-specific metabolites.

12. Si-Jia Wang#, Zi-Xi Fu#, Wei-Bing Chen, Si-Tong Wu, Song-Ze Ke, Jian-Feng Tu*, Bin Wei*. Saccharina japonica polysaccharides suppress high-fat diet-induced obesity and modulate gut microbiota composition and function. Chemistry & Biodiversity (2024), e20241088. (https://doi.org/10.1002/cbdv.202401088)

Abstract

Recent studies have highlighted the potential of Saccharina japonica Polysaccharides (SJPs) in alleviating high-fat diet (HFD)-induced obesity by regulating gut microbiota, which warrants further exploration to elucidate the underlying structure-activity relationship. In this study, five polysaccharide fractions (Sj−T, Sj−T-1, Sj−T-2, Sj−T-3, and Sj−T-4) with different structure characteristics were prepared from S. japonica, and their effects on HFD-induced obesity and gut microbiota composition were investigated using C57BL/6J mice. The results revealed that oral administration of Sj−T considerably suppressed HFD-induced obesity, glucose metabolic dysfunction, and other disordered symptoms. While, Sj−T-2, which has the lowest molecular weight, was the most effective in alleviating HFD-induced obesity and had the second-best effect on improving HFD-induced impaired glucose tolerance among the five SJPs. Supplementation with SJPs significantly modulated HFD-induced gut microbiota dysbiosis both at the phylum and species levels, such as enriching Desulfobacterota and Actinobacteriota, while suppressing the abundance of Bacteroidota. Sj−T also dramatically restored the gut microbiota composition by modulating the abundance of many crucial gut bacterial taxa, including s_Bacteroides_acidifaciens, s_Lachnospiraceae _bacterium, and g_Lachnospiraceae_NK4A136_group. Besides, SJPs also dramatically altered the function of gut microbiota, including many carbohydrate-metabolism enzymes. This study highlights the potential of SJPs in preventing obesity and restoring intestinal homeostasis in obese individuals.

13. Wei-Bing Chen#, Gang-Ao Hu#, Bing-Cheng Dong, Huai-Ying Sun, Dong-Ze Lu, Meng-Ying Ru, Yan-Lei Yu, Hong Wang*, Bin Wei*. Insignhts into the modulatory effects of host-gut microbial xanthine co-metabolism on high-fat diet-fed mice. Biochemical Pharmacology (2024), 230(1), 116596. (https://doi.org/10.1016/j.bcp.2024.116596)

ABSTRACT

Gut microbiota-mediated endobiotic and xenobiotic metabolism play crucial roles in disease progression, and drug therapy/toxicity. Our recent study suggested that gut microbiota-mediated xanthine metabolism is correlated with resistance to high-fat diet (HFD)-induced obesity. Here, we explored the role of host-gut microbial xanthine co-metabolism in the prevention and treatment of HFD-induced obesity by orally administration of Bifidobacterium longum, xanthine, and a xanthine oxidase inhibitor (topiroxostat). The findings indicate that xanthine exhibits a significantly protective effect against HFD-induced obesity. While B. longum, xanthine, and topiroxostat did not alleviate the dysbiosis of the weight and glucose metabolism of HFD-induced obesity (DIO) and obesity resistance (DIR) mice. 16S rRNA sequencing analyses revealed that treatments with B. longum significantly altered gut microbiota composition in HFD-fed and DIO mice. Microbial interaction network analysis revealed several Bacteroidetes species, such as Amulumruptor caecigallinarius and Muribaculum intestinale, as keystone taxa that were notably enriched by B. longum. Untargeted metabolomics analysis implied that xanthine might serve as a crucial molecule in regulating body weight, exerting a preventive effect on HFD-induced obesity. This study offers new perspectives on the influence of host-gut microbial xanthine co-metabolism on HFD-fed mice and emphasizes the promising role of xanthine in promoting weight loss.

14. Cancan Wang#, Chenjie Wang#, Yanjun Liu, Yujie Yue, Xingyue Lu, Hong Wang, Youmin Ying*, Jianwei Chen*. Targeted discovery of polyketides with antioxidant activity through integrated omics and cocultivation strategies. Applied Environmental and Microbiology. 2024, 90, 11. (https://doi.org/10.1128/aem.01603-24)

ABSTRACT 

Fungi generate a diverse array of bioactive compounds with significant pharmaceutical applications. However, the chemical diversity of natural products in fungi remains largely unexplored. Here, we present a paradigm for specifically discovering diverse and bioactive compounds from fungi by integrating genome mining with building block molecular network and coculture analysis. Through pangenome and sequence similarity network analysis, we identified a rare type I polyketide enzyme from Penicillium sp. ZJUT-34. Subsequent building block molecular network and coculture strategy led to the identification and isolation of a pair of novel polyketides, (±)-peniphenone E [(±)−1], three known polyketides (2–4), and three precursor compounds (5–7) from a combined culture of Penicillium sp. ZJUT-34 and Penicillium sp. ZJUT23. Their structures were established through extensive spectroscopic analysis, including NMR and HRESIMS. Chiral HPLC separation of compound 1 yielded a pair of enantiomers(+)−1 and (−)−1, with their absolute configurations determind using calculated ECD methods. Compound (±)−1 is notable for its unprecedented structure, featuring a unique 2-methyl-hexenyl-3-one moiety fused with a polyketide clavatol core. We proposed a hypothetical biosynthetic pathway for (±)−1. Furthermore, compounds 2, 5, and 6 exhibited strong antioxidant activity, whereas (−)−1, (+)−1, 3, and 4 exhibited moderate antioxidant activity compared to the positive control, ascorbic acid. Our research demonstrates a pioneering strategy for uncovering novel polyketides by merging genome mining, metabolomics, and cocultivation methods. This approach addresses the challenge of discovering natural compounds produced by rare biosynthetic enzymes that are often silent under conventional conditions due to gene regulation.

15. Wentao Wu, Esther Cai Xia Ang, Xinru Xu, Qi Wang, Hong Wang*, Richmond Lee*, Choon-Hong Tan*, Xinyi Ye*. Asymmetric N-oxidation catalyzed by bisguanidinium dinuclear oxodiperoxomolybdosulfate. Nature Communications. 2024, 15: 7317. (https://doi.org/10.1038/s41467-024-51765-0)

Abstract

N-oxides play a pivotal role in natural products and emerging drug design, while also serving as valuable ligand scaffolds in organometallic chemistry. Among heteroatom oxidations, the conversion of amines to N-oxides is a critical and challenging facet. We present here a highly enantioselective N-oxidation methodology for both cyclic and acyclic amines. The method employs an ion-pair catalyst comprising a chiral bisguanidinium [BG] 2+ cation and an achiral oxodiperoxomolybdosulfate anion [(µ-SO4)2Mo2O2(µ-O2)2(O2)2] 2-. Notably, the bisguanidinium cation undergoes modification through silyl group incorporation and is elucidated by X-ray crystallography. Our findings underscore the crucial role of the side chain in the determination of the chiral pocket size, allowing for the oxidation of diverse tertiary amines with enantioselectivities. Comprehensive mechanistic investigations are conducted to explain the catalytic system’s efficacy in achieving dynamic kinetic resolution (DKR) with high efficiency.

16. Lewen Wu, Choon-Hong Tan*, Xinyi Ye. Applications of Antimony in Catalysis. Organic & Inorganic Au. 2024. (https://pubs.acs.org/doi/10.1021/acsorginorgau.4c00072?ref=pdf)

Abstract

Antimony is a fifth-period element in the nitrogen family, a silver-white metalloid with weak conductivity and thermal conductivity. It is stable at room temperature and does not react easily with oxygen and water in the air. Natural minerals are found in the form of sulfides. Current research and applications are mostly concentrated on material modification, utilizing the properties of antimony in traditional chemical industries, helping alloys improve their flame retardancy, stability, increasing semiconductor performance, etc. For example, to enhance the electronic conductivity, after coating or embedding antimony or its derivatives in thin layers in photonic nanomaterials, the performance of the original material in photoelectrochemical catalysis can be effectively increased, thereby expanding the efficiency of oxidation−reduction reactions accounting for the degradation of organic matter in wastewater. However, the catalytic reaction between the derivatives of antimony and organic compounds beside the material is less studied, and the mechanism of the studies in organic synthesis is relatively unclear. The reported organic synthesis related to antimony is mainly in the form of Lewis acid catalysts or dual-metal catalytic systems combined with other metals. This Review will focus on the application of antimony in photocatalysis, electrocatalysis, and other organic syntheses in the past 10 years.

17. Qiaoqiang Li, Yuqiang Dai, Xinru Xu, Wentao Wu, Wenchao Chen, Hong Wang, Choon-Hong Tan*, Xinyi Ye*. Enantioselective reduction and sulfenylation of isoflavanone derivatives via bisguanidinium hypervalent silicate. Org. Lett. 2024, 26, 6241−6246. (https://doi.org/10.1021/acs.orglett.4c02202)

Abstract

In this work, we describe an enantioselective reduction and sulfenylation of isoflavanone derivatives by an ion pair strategy. The chiral cationic catalyst bisguanidinium (BG) is capable of chiral induction in catalytic systems. Silane hydride works as a reductant and helps to form an anionic hypervalent silicate complex and intermediates with substrates to pair with chiral catalyst. A series of umpolung sulfur reagents accomplish electrophilic attack in the presence of a silicate anion. Both chemoselectivity and enantioselectivity are good to excellent to afford a wide scope of 4-oxo-4H-chromene-3-carbonitrile and S-electrophilic reagents. Further transformations were completed to introduce more applications.

18. Yue Wei, Guishun Bai, Jiamin Wu, Yi Hua, Tao Zhang, Congyong Yue, Hong Wang, Xiaoze Bao*. Enantioselective addition of3-hydroxyquinolin-2(1H)-one to isatin and pyrazole-4,5-dione derived ketimines. Organic Chemistry Frontiers. 2024, DOI: (https://doi.org/10.1039/D4QO01895H)

ABSTRACT 

The enantioselective reactivity of 3-hydroxyquinolin-2(1H)-oneswas developed through their addition to isatin and pyrazole-4,5-dione derivedketimines, affording novel architectures featuring multiple natural productscaffolds in high yields with excellent enantioselectivities. Gram-scalesynthesis and synthetic transformations further disclosed the potential of thecurrent process.

19. Zhiyang Fu, Xiangzhou Gong, Zhe Hu, Yujie Zhao, Huawei Zhang. Phenolic bisabolane sesquiterpene derivatives from an Arctic marine-derived fungus Aspergillus sydowii MNP-2. Natural Products Journal. 2024, 14(7): 10-16. (https://doi.org/10.2174/0122103155279752240104050411)

ABSTRACT 

Filamentous fungi in the genus Aspergillus are well known for their important roles in the production of bioactive secondary metabolites with diverse chemical structures and potential applications in the pharmaceutical industry. In this work, chemical investigation of an Arctic marine-derived strain A. sydowii MNP-2, led to the isolation of 11 phenolic bisabolane-type sesquiterpenes (PBSs, 1- 11) using various chromatographic methods. Their chemical structures were unambiguously determined by 1 H NMR spectroscopy and mass spectrometry analyses as well as comparison with literature data. It is noteworthy that compounds 1, 7 and 11 were first obtained from A. sydowii. Antimicrobial assay showed that these chemicals had no potent inhibitory effect on Staphylococcus aureus, Escherichia coli, and Candida albicans with MIC values > 16 µg/mL. Additionally, the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced inflammation in mouse macrophages (RAW264.7) and BV2 microglial cells were all below 10% for compounds 4-6 and 8, indicating almost negligible anti-inflammatory efficacy. Among the tested compounds 4-6 and 8 for tumor-cell proliferation inhibition activities, compound 5 demonstrated the strongest inhibitory effect against human acute promyelocytic leukemia cells (HL-6) with a 44.76% inhibition rate.

20. Zijun Liu ,Wenyan Sun, Zhe Hu, Wei Wang, Huawei Zhang*. Marine Streptomyces-Derived Novel Alkaloids Discovered in the Past Decade. Marine Drugs. 2024, 22 (1):51. (https://doi.org/10.3390/md22010051)

ABSTRACT 

Natural alkaloids originating from actinomycetes and synthetic derivatives have always been among the important suppliers of small-molecule drugs. Among their biological sources, Streptomyces is the highest and most extensively researched genus. Marine-derived Streptomyces strains harbor unconventional metabolic pathways and have been demonstrated to be efficient producers of biologically active alkaloids; more than 60% of these compounds exhibit valuable activity such as antibacterial, antitumor, anti-inflammatory activities. This review comprehensively summarizes novel alkaloids produced by marine Streptomyces discovered in the past decade, focusing on their structural features, biological activity, and pharmacological mechanisms. Future perspectives on the discovery and development of novel alkaloids from marine Streptomyces are also provided.

21. Ziwei Huang, Wangjie Zhu, Yifan Bai, Xuelian Bai, Huawei Zhang*. Non-ribosomal peptide synthetase (NRPS)-encoding products and their biosynthetic logics in Fusarium. Microbial Cell Factories. 2024, 23: 93. (DOI:10.1186/s12934-024-02378-1)

ABSTRACT 

 Fungal non-ribosomal peptide synthetase (NRPS)-encoding products play a paramount role in new drug discovery. Fusarium, one of the most common filamentous fungi, is well-known for its biosynthetic potential of NRPS-type compounds with diverse structural motifs and various biological properties. With the continuous improvement and extensive application of bioinformatic tools (e.g., anti-SMASH, NCBI, UniProt), more and more biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) have been identified in Fusarium strains. However, the biosynthetic logics of these SMs have not yet been well investigated till now. With the aim to increase our knowledge of the biosynthetic logics of NPRS-encoding products in Fusarium, this review firstly provides an overview of research advances in elucidating their biosynthetic pathways.