Design, synthesis, and biological evaluation of β-carboline derivatives as ABCB1 inhibitors for reversing multidrug resistance.

The scarcity of ATP-binding cassette subfamily B member 1 (ABCB1, also known as P-glycoprotein, P-gp) inhibitors suitable for clinical application in improving multidrug resistance (MDR) promotes the development of drugs aimed at reversing MDR. In this work, we reported a comprehensive study for the first time about the reversal activity of β-carboline derivatives on ABCB1-mediated MDR. Among 48 synthesized derivatives, compound K27 significantly increased the sensitivity of ABCB1-mediated MDR SW620/AD300 cells to paclitaxel (PTX) (IC = 15.

Butyrolactone I blocks the transition of acute kidney injury to chronic kidney disease in mice by targeting JAK1.

Chronic kidney disease (CKD) is a disease that affects more than 850 million people. Acute kidney injury (AKI) is a common cause of CKD, and blocking the AKI-CKD transition shows promising therapeutic potential. Herein, we found that butyrolactone I (BLI), a natural product, exerts significant nephroprotective effects, including maintenance of kidney function, inhibition of inflammatory response, and prevention of fibrosis, in both folic acid- and ureteral obstruction-induced AKI-CKD transition mouse models.

Bipolaristeroid A, a 5,6-seco-9,10-seco-steroid with cytotoxic activity from the fungus Bipolaris maydis.

Eleven undescribed steroids, bipolaristeroids A-K, and one known compound, demethylincisterol A, were isolated from the fungus Bipolaris maydis. Bipolaristeroid A is a 5,6-seco-9,10-seco-steroid with a rearranged B ring, in which the A and C rings are connected by an ester bond. Bipolaristeroid B is a rearranged 1(10 → 6)-abeosteroid with an aromatic B ring.

Maydisens, Sesterterpenoids with Anti-MDR Activity from .

Fourteen previously undescribed sesterterpenoids (-) were isolated from . Their structures with absolute configurations were elucidated by NMR, HRESIMS, DP4+ calculations, ECD calculations, single-crystal X-ray diffraction analyses, and the modified Mosher's method. Compounds - possess an uncommon 5/11 bicyclic ring system identified from for the first time.

Michael Acceptor Pyrrolidone Derivatives and Their Activity against Diffuse Large B-cell Lymphoma.

Objective: This study aimed to design and evaluate the efficacy of pyrrolidone derivatives as potential therapeutic agents against diffuse large B-cell lymphoma (DLBCL), a common and heterogeneous malignancy of the adult lymphohematopoietic system. Given the limitations of current therapies, there is a pressing need to develop new and effective drugs for DLBCL treatment.

Methods: A series of pyrrolidone derivatives were synthesized, and their antitumor activities were assessed, particularly against DLBCL cell lines.

Ten ring-B aromatized ergosterols from Aspergillus spectabilis.

Spectasterols F-O (1-10), ten interesting ergosterols with an aromatized B ring, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined using a combination of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, single-crystal X-ray diffraction analyses, and electronic circular dichroism (ECD) calculations. Structurally, these aromatic ergosterols feature versatile side chains.

Chaetoxylariones A-G: undescribed chromone-derived polyketides from co-culture of Chaetomium virescens and Xylaria grammica enabled via the molecular networking strategy.

By co-culturing two endophytic fungi (Chaetomium virescens and Xylaria grammica) collected from the medicinal and edible plant Smilax glabra Roxb. and analyzing them with MolNetEnhancer module on GNPS platform, seven undescribed chromone-derived polyketides (chaetoxylariones A-G), including three pairs of enantiomer ones (2a/2b, 4a/4b and 6a/6b) and four optical pure ones (1, 3, 5 and 7), as well as five known structural analogues (8-12), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray diffraction, C NMR calculation and DP4+ probability analyses, as well as the comparison of the experimental electronic circular dichroism (ECD) data.

Maydistacins A-G, Terpestacin-type Sesterterpenoids with Anti-inflammatory Activity from the Phytopathogenic Fungus .

Seven undescribed terpestacin-type sesterterpenoids, maydistacins A-G (-), along with two known congeners ( and ), were isolated from the phytopathogenic fungus collected from the leaves of . The structures of - were elucidated based on extensive spectroscopic analysis, chemical methods, NMR calculations with DP4+ probability analysis, and comparison of experimental and calculated electronic circular dichroism (ECD) calculations. anti-inflammatory effects of these compounds were tested in lipopolysaccharide (LPS)-stimulated RAW264.

Discovery of bioactive polycyclic polyprenylated acylphloroglucinols with adamantine/homoadamantane skeletons from Hypericum wilsonii.

In this work, nine previous undescribed polycyclic polyprenylated acylphloroglucinols with adamantine/homoadamantane skeletons, cumilcinols A-I (1-9), along with six known analogues, were isolated and identified from the stems, leaves and flowers of Hypericum wilsonii. Their structures were determined by HRESIMS, NMR spectroscopic analysis, single-crystal X-ray crystallography as well as electronic circular dichroism calculations and comparisons. Compound 2 formed a unique furan ring bearing a rare acetal functionality.

Spectasterols, Aromatic Ergosterols with 6/6/6/5/5, 6/6/6/6, and 6/6/6/5 Ring Systems from .

Spectasterols A-E (-), aromatic ergosterols with unique ring systems, were isolated from . Compounds and possess a 6/6/6/5/5 ring system with an additional cyclopentene, while and have an uncommon 6/6/6/6 ring system generated by the D-ring expansion via 1,2-alkyl shifts. Compound exhibited cytotoxic activity (IC 6.

ERK Inhibition Promotes Engraftment of Allografts by Reprogramming T-Cell Metabolism.

Extracellular regulated protein kinases (ERK) signaling is a master regulator of cell behavior, life, and fate. Although ERK pathway is shown to be involved in T-cell activation, little is known about its role in the development of allograft rejection. Here, it is reported that ERK signaling pathway is activated in allograft-infiltrating T cells.

Collective synthesis of aspulvinone and its analogues by vinylogous aldol condensation of substituted tetronic acids with aldehydes.

A mild, modular and efficient synthetic method with broad substrate scope was developed for aspulvinones. Nine natural aspulvinones were synthesized, six of which were for the first time. The aldol condensation delivered -configuration products predominantly in MeCN.

KSO-Mediated Radical Cyclization of 1,6-Enyne for the Synthesis of Diiodonated γ-Lactams.

A novel and convenient KSO-mediated diiodo cyclization of 1,6-enynes for the facile synthesis of functionalized γ-lactam derivatives has been developed. This reaction features mild and transition-metal-free conditions, which offer a green and efficient entry to synthetically important γ-lactam scaffolds. Mechanistic studies suggest that iodide radicals initiate the cascade cyclic transformation.

A novel Gboxin analog induces OXPHOS inhibition and mitochondrial dysfunction-mediated apoptosis in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell non-Hodgkin's lymphoma. Currently, moderate efficacy and limitations of approved drugs still exist, and it is necessary to develop newer and more effective drugs. Gboxin is a promising inhibitor of OXPHOS, which specifically inhibits the growth of many kinds of cancer cell lines.

A new diketopiperazine-type alkaloid from the endophytic fungus .

A chemical investigation on an endophytic fungus isolated from the medicinal plant Willd. (Plantaginaceae) afforded one new diketopiperazine-type alkaloid, namely penicimine A (), as well as two known congeners ( and ). Their structures were elucidated by widespread spectroscopic data, and the absolute configurations of and were further confirmed by single-crystal X-ray diffraction analyses.

A Removable Acyl Group Promoted the Intramolecular Dehydro-Diels-Alder Reaction of Styrene-Ynes: Highly Chemoselective Synthesis of Aryldihydronaphthalene Derivatives.

A removable acyl group promoted the intramolecular didehydro-Diels-Alder reaction of styrene-ynes under mild reaction conditions is proposed. The reaction is free of metals and catalysts, is easy to perform, and exhibits good functional group tolerance, providing a highly chemoselective approach for obtaining the valuable aryldihydronaphthalene derivatives.

Isolation, absolute configurations and bioactivities of pestaphilones A-I: Undescribed methylated side chain containing-azaphilones from Pestalotiopsis oxyanthi.

Nine undescribed side chain containing azaphilones, pestaphilones A-I, were isolated from the Anoectochilus roxburghii endophytic fungus Pestalotiopsis oxyanthi. The structures of these isolates were identified by spectroscopic data, electronic circular dichroism (ECD) calculations and comparisons, quantum-chemical C NMR calculations with DP4+ probability analysis, Rh(OCOCF)-induced ECD, acetonide formation, selective oxidation reaction and X-ray crystallographic data. Structurally, pestaphilones A-I were the first azaphilones characteristically formed via a methyl group at C-9 in the C side chain.

Discovery of GOT1 Inhibitors from a Marine-Derived That Act against Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a devastating digestive system carcinoma with high incidence and death rates. PDAC cells are dependent on the Gln metabolism, which can preferentially utilize glutamic oxaloacetate transaminase 1 (GOT1) to maintain the redox homeostasis of cancer cells. Therefore, small molecule inhibitors targeting GOT1 can be used as a new strategy for developing cancer therapies.

Spectanoids A-H: Eight undescribed sesterterpenoids from Aspergillus spectabilis.

Ten sesterterpenoids, including eight undescribed ones named spectanoids A-H and two known analogs, were obtained from Aspergillus spectabilis. Their structures, including absolute configurations, were determined based on HRESIMS, NMR, ECD calculations and single-crystal X-ray diffraction analyses. Spectanoids A-G are tricyclic sesterterpenoids with an unusual 5/12/5 ring system, while spectanoid H possesses a 5/8/6/5 ring system.

Bipolaquinones A-J, Immunosuppressive Meroterpenoids from a Soil-Derived .

Ten new meroterpenoids, bipolaquinones A-J (-), and one known congener, isocochlioquinone F (), were isolated and identified from the fermented rice cultures of a soil-derived fungus, . The planar structures of - were elucidated based on extensive spectroscopic analyses (including HRESIMS and 1D and 2D NMR data), and their absolute configurations were determined by single-crystal X-ray diffraction analyses, comparison of experimental electronic circular dichroism (ECD) data, ECD calculations, and hydrolysis reaction. The immunosuppressive activity assay revealed that compounds , , and - showed significant inhibitory activity against concanavalin A (ConA)-induced T lymphocyte proliferation with IC values ranging from 4.

Synthesis of Succinimides via Intramolecular Alder-Ene Reaction of 1,6-Enynes.

A novel and convenient method has been developed for the facile synthesis of functionalized succinimide derivatives via intramolecular Alder-ene reaction of 1,6-enynes. This reaction features mild and metal-free reaction conditions, which offers a green and efficient entry to synthetically important succinimide scaffolds. Preliminary mechanistic studies suggest that a diradical intermediate might be involved in this transformation.

Progress in the Chemistry of Cytochalasans.

Cytochalasans are a group of fungal-derived natural products characterized by a perhydro-isoindolone core fused with a macrocyclic ring, and they exhibit a high structural diversity and a broad spectrum of bioactivities. Cytochalasans have attracted significant attention from the chemical and pharmacological communities and have been reviewed previously from various perspectives in recent years. However, continued interest in the cytochalasans and the number of laboratory investigations on these compounds are both growing rapidly.

Longisglucinols A-C, Structurally Intriguing Polycyclic Polyprenylated Acylphloroglucinols with Anti-inflammatory Activity from .

Longisglucinol A (), a polycyclic polyprenylated acylphloroglucinol (PPAP) with a new skeleton, along with two new congeners, longisglucinols B () and C (), were isolated from . Compound features an unparalleled 6/6/6/5 fused ring skeleton based on a unique 8-oxa-tetracyclo-[8.3.