Discovery of a Chimeric Polyketide Family as Cancer Immunogenic Chemotherapeutic Leads.

Discovery of cancer immunogenic chemotherapeutics represents an emerging, highly promising direction for cancer treatment that uses a chemical drug to achieve the efficacy of both chemotherapy and immunotherapy. Herein, we report a high-throughput screening platform and the subsequent discovery of a new class of cancer immunogenic chemotherapeutic leads. Our platform integrates informatics-based activity metabolomics for the rapid identification of microbial natural products with both novel structures and potent activities.

Discovery of A Chimeric Polyketide Family as Cancer Immunogenic Chemotherapeutic Leads.

Discovery of cancer immunogenic chemotherapeutics represents an emerging, highly promising direction for cancer treatment that uses a chemical drug to achieve the efficacy of both chemotherapy and immunotherapy. Herein we report a high-throughput screening platform and the subsequent discovery of a new class of cancer immunogenic chemotherapeutic leads. Our platform integrates informatics-based activity metabolomics for rapid identification of microbial natural products with both novel structures and potent activities.

Design, synthesis, and biological evaluation of (thio)urea derivatives as potent -glucuronidase inhibitors.

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, synthesised, and biologically assayed. The bioassay results revealed that (IC = 2.

Vanadium-Doped Heterogeneous Bimetallic Phosphides Derived from Layered Double Hydroxides for Saline Water Splitting.

The development of energy- and time-saving synthetic methods to prepare bifunctional and high stability catalysts are vital for overall water splitting. Here, V-doped nickel-iron hydroxide precursor by etching NiFe foam (NFF) at room temperature with dual chloride solution ("NaCl-VCl3"), is obtained then phosphating to obtain V-NiP-FeP/NFF as efficient bifunctional (oxygen/hydrogen exchange reaction, OER/HER) electrocatalysts, denoted as NFF(V, Na)-P. The NFF(V, Na)-P requires only 185 and 117 mV overpotentials to reach 10 mA cm for OER and HER.

Proof-of-concept studies with a computationally designed M inhibitor as a synergistic combination regimen alternative to Paxlovid.

As the SARS-CoV-2 virus continues to spread and mutate, it remains important to focus not only on preventing spread through vaccination but also on treating infection with direct-acting antivirals (DAA). The approval of Paxlovid, a SARS-CoV-2 main protease (M) DAA, has been significant for treatment of patients. A limitation of this DAA, however, is that the antiviral component, nirmatrelvir, is rapidly metabolized and requires inclusion of a CYP450 3A4 metabolic inhibitor, ritonavir, to boost levels of the active drug.

Design, synthesis, and bioactivity evaluation of novel indole-selenide derivatives as P-glycoprotein inhibitors against multi-drug resistance in MCF-7/ADR cell.

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.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion.

Background: Impaired glucose tolerance (IGT) is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes. When IGT occurs, insulin sensitivity decreases, causing a reduction in insulin secretion and an increase in glucagon secretion. Recently, vascular endothelial growth factor B (VEGFB) has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.

A marine-derived fatty acid targets the cell membrane of Gram-positive bacteria.

With the lack of new antibiotics in the drug discovery pipeline, coupled with accelerated evolution of antibiotic resistance, new sources of antibiotics that target pathogens of clinical importance are paramount. Here, we use bacterial cytological profiling to identify the mechanism of action of the monounsaturated fatty acid ()-13-methyltetra-4-decenoic acid isolated from the marine bacterium with antibacterial effects against Gram-positive bacteria. The fatty acid antibiotic was found to rapidly destabilize the cell membrane by pore formation and membrane aggregation in , suggesting that this fatty acid may be a promising adjuvant used in combination to enhance antibiotic sensitivity.

N,S co-doped porous carbon with CoS prepared with a Co-FF-derived CoO template: a bi-functional electrocatalyst for rechargeable zinc-air batteries.

To achieve broad commercialization of rechargeable metal-air batteries, the development of non-precious metal-based bi-functional oxygen electrocatalysts is critical. In this study, we prepared N,S co-doped porous carbon materials containing CoS nanoparticles (CoS/NSC) through a one-step pyrolysis process. The process involved the pyrolysis of a polydopamine (PDA) coated Co-formic acid framework (Co-FF) derived CoO and thiourea.

Vascular endothelial growth factor B regulates insulin secretion in β cells of type 2 diabetes mellitus mice via PLCγ and the IP3R‑evoked Ca2/CaMK2 signaling pathway.

Vascular endothelial growth factor B (VEGFB) plays a crucial role in glucolipid metabolism and is highly associated with type 2 diabetes mellitus (T2DM). The role of VEGFB in the insulin secretion of β cells remains unverified. Thus, the present study aimed to discuss the effect of VEGFB on regulating insulin secretion in T2DM development, and its underlying mechanism.

Evaluating the Patient Boarding during Omicron Surge in Hong Kong: Time Series Analysis.

The fifth wave of COVID-19 outbreaks in Hong Kong (HK) from January to March 2022 has the highest confirmed cases and deaths compared with previous waves. Severe hospital boarding (to inpatient wards) was noted in various Emergency Departments (EDs). Our objective is to identify factors associated with hospital boarding during Omicron surge in HK.

Rapid Unambiguous Structure Elucidation of Streptnatamide A, a New Cyclic Peptide Isolated from A Marine-derived Streptomyces sp.

Cyclic peptides have been excellent source of drug leads. With the advances in discovery platforms, the pharmaceutical industry has a growing interest in cyclic peptides and has pushed several into clinical trials. However, structural complexity of cyclic peptides brings extreme challenges for structure elucidation efforts.

Global analysis of the biosynthetic chemical space of marine prokaryotes.

Background: Marine prokaryotes are a rich source of novel bioactive secondary metabolites for drug discovery. Recent genome mining studies have revealed their great potential to bio-synthesize novel secondary metabolites. However, the exact biosynthetic chemical space encoded by the marine prokaryotes has yet to be systematically evaluated.

Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell.

P-glycoprotein (P-gp) is one of the drug efflux transporters that triggers multidrug resistance (MDR) in cells. Herein, by utilizing the strategies of active skeleton splicing and structural optimization on the lead compound 5 m, a total of 50 novel 2,5-disubstituted furan derivatives were designed, synthesized, and screened for P-gp inhibitory activity. The structure-activity relationship analysis enabled the identification of an important pharmacophore N-phenylbenzamide, which resulted in the discovery of a promising drug lead compound Ⅲ-8.

Discovery of New Siderophores from a Marine sp. via Combined Metabolomics and Analysis of Iron-Chelating Activity.

The marine-derived sp. FIMYZ-003 strain was found to produce novel siderophores with yields negatively correlated with the iron concentration in the medium. Mass spectrometry (MS)-based metabolomics coupled with metallophore assays identified two novel α-hydroxycarboxylate-type siderophores, fradiamines C and D ( and ), together with two related known siderophores, fradiamines A and B ( and ).

Novel Benzo Five-Membered Heterocycle Derivatives as P-Glycoprotein Inhibitors: Design, Synthesis, Molecular Docking, and Anti-Multidrug Resistance Activity.

A proposed strategy to overcome multidrug resistance (MDR) of anticancer drugs in chemotherapy is to disable the efflux function of P-glycoprotein (P-gp). In this study, based on ring-merging and fragment-growing strategies, 105 novel benzo five-membered heterocycle derivatives were designed, synthesized, and screened. Exploration of the structure-activity relationship (SAR) led to the identification of with low cytotoxicity and promising reversal activity to doxorubicin in MCF-7/ADR cells.

The Soft Coral : A Warehouse of Terpenoids with Structural and Pharmacological Diversity.

The soft coral , which was frequently encountered on Indo-Pacific and Red Sea coral reefs, furnished a wealth of secondary metabolites. Notably, terpenoids dominated the chemical profile of this species. In this review, we summarized the discovery of 156 terpenoids from the soft coral specimens in different geographical areas.

Design, synthesis and biological evaluation of novel phenylfuran-bisamide derivatives as P-glycoprotein inhibitors against multidrug resistance in MCF-7/ADR cell.

The co-administration of anticancer drugs and P-glycoprotein (P-gp) inhibitors was a treatment strategy to surmount multidrug resistance (MDR) in anticancer chemotherapy. In this study, novel phenylfuran-bisamide derivatives were designed as P-gp inhibitors based on target-based drug design, and 31 novel compounds were synthesized and screened on MCF-7/ADR cells. The result of bioassay revealed that compound y12d exhibited low cytotoxicity and promising MDR reversal activity (IC = 0.

Guided Isolation of An Uncommon Cembranoid Orthoester, Sarcotortin A, and Three Skeletal Diverse Terpenoids from the Hainan Soft Coral Sarcophyton tortuosum Based on Molecular Networking Strategy.

Applying the emerging molecular networking strategy, an uncommon cembranoid orthoester, sarcotortin A (1), featuring a 3/14/8/5-fused scaffold, an unusual eunicellane-type diterpenoid, sarcotorolide A (2), and two new biscembranoids, ximaolides M and N (7 and 8), along with nine known terpenoids 3-6 and 9-13 were isolated from the Hainan soft coral Sarcophyton tortuosum. The structure and absolute configuration of all new compounds were established by a combination of spectroscopic data, X-ray diffraction analysis, and/or quantum chemical computational approaches. The plausible biogenetic relationship among these skeletally different terpenoids was proposed and discussed.

Metabolomics and Genomics Enable the Discovery of a New Class of Nonribosomal Peptidic Metallophores from a Marine .

Although microbial genomes harbor an abundance of biosynthetic gene clusters, there remain substantial technological gaps that impair the direct correlation of newly discovered gene clusters and their corresponding secondary metabolite products. As an example of one approach designed to minimize or bridge such gaps, we employed hierarchical clustering analysis and principal component analysis (, whose sole input is MS data) to prioritize 109 marine strains and ultimately identify novel strain WMMB482 as a candidate for in-depth "metabologenomics" analysis following its prioritization. Highlighting the power of current MS-based technologies, not only did enable the discovery of one new, nonribosomal peptide bearing an incredible diversity of unique functional groups, but metabolomics for WMMB482 unveiled 16 additional congeners via the application of Global Natural Product Social molecular networking (GNPS), herein named ecteinamines A-Q (-).

Ocellatuperoxides A-F, Uncommon Anti-Tumoral -Pyrone Peroxides from a Photosynthetic Mollusk .

Six new pairs of -pyrone polypropionate enantiomers with an unusual peroxyl bridge at the side chain, namely (±)-ocellatuperoxides A-F (-), were isolated and characterized from the South China Sea photosynthetic mollusk . Extensive spectroscopic analysis, single crystal X-ray diffraction analysis, ECD- (electronic circular dichroism) comparison, and TDDFT (time-dependent density functional theory) ECD computation were used to determine the structures and absolute configurations of new compounds. In a cell viability assay, several compounds showed considerable anti-tumoral effects on human non-small cell lung cancer cells A549 with Gefitinib (7.

A Small-Molecule Inhibitor of the Anthranilyl-CoA Synthetase PqsA for the Treatment of Multidrug-Resistant Pseudomonas aeruginosa.

One of the challenges associated with the treatment of Pseudomonas aeruginosa infections is the high prevalence of multidrug resistance (MDR). Since conventional antibiotics are ineffective at treating such bacterial infections, innovative antibiotics acting upon novel targets or via mechanisms are urgently required. In this study, we identified a quorum sensing inhibitor (QSI), norharmane, that uniquely shows weak antibacterial activity but strongly inhibits pyocyanin production and biofilm formation of MDR P.

Bacillimidazoles A-F, Imidazolium-Containing Compounds Isolated from a Marine .

Chemical investigations of a marine sponge-associated revealed six new imidazolium-containing compounds, bacillimidazoles A-F (-). Previous reports of related imidazolium-containing natural products are rare. Initially unveiled by timsTOF (trapped ion mobility spectrometry) MS data, extensive HRMS and 1D and 2D NMR analyses enabled the structural elucidation of -.

Phenyl-Lactic Acid Is an Active Ingredient in Bactericidal Supernatants of Lactobacillus crispatus.

Lactobacillus crispatus is a well-established probiotic with antimicrobial activity against pathogens across several niches of the human body generally attributed to the production of bacteriostatic molecules, including hydrogen peroxide and lactic acid. Here, we show that the cell-free supernatants of clinical isolates of L. crispatus harbor robust bactericidal activity.

Discovery of anti-infective adipostatins through bioactivity-guided isolation and heterologous expression of a type III polyketide synthase.

Antibiotic resistance and emerging viral pandemics have posed an urgent need for new anti-infective drugs. By screening our microbial extract library against the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the notorious ESKAPE pathogens, an active fraction was identified and purified, leading to an initial isolation of adipostatins A (1) and B (2). In order to diversify the chemical structures of adipostatins toward enhanced biological activities, a type III polyketide synthase was identified from the native producer, Streptomyces davawensis DSM101723, and was subsequently expressed in an E.