Synthesis and in-silico Studies of 4-phenyl thiazol-2-amine Derivatives as Putative Anti-breast Cancer Agents.

BACKGROUND: Breast cancer (BC) is the second-leading cause of cancer-related fatalities in women after lung cancer worldwide. The development of BC is significantly influenced by estrogen receptors (ERs). The problem with current cancer treatments is selectivity, target specificity, cytotoxicity, and developing resistance. Thiazole scaffolds are gaining popularity in drug discovery due to their broad range of biological activity. It has the extraordinary capacity to control a variety of cellular pathways, and its potential for selective anticancer activity can be explored. OBJECTIVE: Synthesis and in-silico studies of 4-Phenyl thiazol-2-amine derivatives as anti-breast cancer agents and molecular docking was used to assess the compounds' capacity to bind ER-α protein target. METHODS: In this study, 4-Phenylthiazol-2-amine derivatives (3a-j) have been synthesized, and using Schrodinger software, molecular docking and ADME studies of the compounds were conducted. RESULTS: Most of the synthesized compounds have shown dock scores ranging from -6.658 to - 8.911 kcal/mol, which is better than the standard drug tamoxifen (-6.821 kcal/mol). According to molecular docking, all compounds fit in the protein's active site and have the same hydrophobic pocket as the standard drug tamoxifen. Further, all of the compounds' ADME properties are below acceptable limits. CONCLUSION: Compound 3e showed the best docking score of -8.911. All compounds' ADME properties are within acceptable limits, and their p/o coefficients fall within a range, suggesting they will all have sufficient absorption at the site of action. These compounds can be evaluated invitro and in-vivo in the future.

Catalytic One-pot Solvent Free Synthesis, Biological Activity, and Docking Study of New Series of 1, 3-thiazolidine-4-one Derivatives Derived from 2- (P-tolyl) Benzoxazol-5-amine.

OBJECTIVE: In this study, a simple triethylammonium salt of phosphoric acid (triethylammonium dihydrogen phosphate) (4) in the liquid state was utilized as an inexpensive, efficient one-pot three components, solvent-free synthesis of thiazolidine-4-one derivatives, with good to excellent yields. Techniques such as FT-IR, 1H-NMR, 13C-NMR, 13C-NMR-DEPT-135, and MS. were used for the structural elucidation. The high biotic efficiency of the newly obtained compounds was confirmed by in vitro antimicrobial action against Gram-positive (S. Aureus), Gram-negative bacteria (P. Aeruginosa and E. Coli) and antifungal activity (C. Albicans) via microplate titer dilution technique. Finally, a molecular docking study was performed with a resolved crystal structure of S. Aureus D-alanine alanyl carrier protein ligase (PDB ID: 7VHV). This investigation aimed to synthesize a new series of thiazolidine-4-one derivatives combined with benzoxazole moiety. MATERIAL AND METHODS: Ionic liquid assistance one-pot solvent-free synthesis method used to synthesize a new series of thiazolidine-4-one derivative 10(a-e). RESULTS: Structural identification of new synthesis and biological evaluation via techniques of (IR, 1H-NMR, 13C-NMR, 13C-NMR-DEPT-135, and MS). CONCLUSION: Ionic liquid is utilized as an inexpensive, efficient one-pot three-component solvent-free synthesis of thiazolidine-4-one derivatives with good to excellent yields. Most of the synthesized compounds showed high biological and anti-fungal activity, in line with the docking study against mentioned microorganism and crystal structure of PDB (ID: 7VHV), respectively.

Casuattimines A-N, fourteen new Lycopodium alkaloids from Lycopodiastrum casuarinoides with Cav3.1 channel inhibitory activity.

Two new dimeric Lycopodium alkaloids, casuattimines A and B (1 and 2), along with twelve previously undescribed Lycopodium alkaloids, casuattimines C-N (3-14), and eight known Lycopodium alkaloids, were isolated from Lycopodiastrum casuarinoides. Casuattimines A and B (1 and 2) are the first two ether-linked Lycopodium alkaloid dimers. Casuattimines C and D (3 and 4) are unique Lycopodium alkaloids characterized by a long fatty acid chain. Structural elucidation was achieved through HRESIMS, NMR, and electronic circular dichroism (ECD) calculations. In addition, the absolute configurations of compounds 7, 13, and 14 were determined by single crystal X-ray diffraction. Compounds 1, 2, and 4 demonstrated notable Cav3.1 channel inhibitory activities presenting IC50 values of 10.75 ± 1.02 µM, 9.33 ± 0.79 µM, and 7.14 ± 0.86 µM, respectively. The dynamics of compound 4 against the Cav3.1 channel and preliminary structure-activity relationships of these active Lycopodium alkaloids were also discussed.

Theoretical insight into the regioselective formation of pyrazolo[1,4]-oxazepine and -oxazines.

AuCl-, AuCl3-, or AuClPEt3-catalyzed formation mechanisms of pyrazolo[1,4]oxazepines and the NaH-promoted mechanism of pyrazolo[1,4]oxazines were investigated computationally. The structural properties of the reactants were studied in various solvents and with different functionals. The hybrid functionals B3LYP, M06, M06-2X, PBEPBE, and wB97X-D in density functional theory were used to determine and discuss the energetics of the compounds. The electronic properties of groups (R = H or R ≠ H) attached to the alkyne moiety played an essential role in the corresponding 7-endo-dig cyclization or 6-exo-dig cyclization in the presence of a gold catalyst. The regioselectivities of the products were investigated, and the natural bond orbitals of the reactants were determined. Furthermore, a gold-catalyzed alternative mechanism is suggested for synthesizing pyrazolo[1,4]oxazines using a terminal alkyne (R = H) moiety as substrate.

Rational design and eco-friendly one-pot multicomponent synthesis of novel ethylidenehydrazineylthiazol-4(5H)-ones as potential apoptotic inducers targeting wild and mutant EGFR-TK in triple negative breast cancer.

A novel series of ethylidenehydrazineylthiazol-4(5H)-ones were synthesized using various eco-friendly one-pot multicomponent synthetic techniques. The anticancer activity of compounds (4a-m) was tested against 11 cancer cell lines. While the IC50 of all compounds was evaluated against the most sensitive cell lines (MDA-MB-468 and FaDu). Our SAR study pinpointed that compound 4a, having a phenyl substituent, exhibited a significant growth inhibition % against all cancer cell lines. The frontier anticancer candidates against the MDA-MB-468 were also examined against the wild EGFR (EGFR-WT) and mutant EGFR (EGFR-T790M) receptors. Most of the synthesized compounds exhibited a higher inhibitory potential against EGFR-T790M than the wild type of EGFR. Remarkably, compound 4k exhibited the highest inhibitory activity against both EGFR-WT and EGFR-T790M with IC50 values (0.051 and 0.021 µM), respectively. The pro-apoptotic protein markers (p53, BAX, caspase 3, caspase 6, caspase 8, and caspase 9) and the anti-apoptotic key marker (BCL-2) were also measured to propose a mechanism of action for the compound 4k as an apoptotic inducer for MDA-MB-468. Investigation of the cell cycle arrest potential of compound 4k was also conducted on MDA-MB-468 cancer cells. We also evaluated the inhibitory activities of compounds (4a-m) against both EGFR-WT and EGFR-T790M using two different molecular docking processes.

Rational design and synthesis of novel quinazolinone N-acetohydrazides as type II multi-kinase inhibitors and potential anticancer agents.

In the current investigation, a new class of quinazolinone N-acetohydrazides 9a-v was designed as type II multi-kinase inhibitors. The target quinazolinones were tailored so that the quinazolinone moiety would occupy the front pocket of the binding sites of VEGFR-2, FGFR-1 and BRAF kinases, meanwhile, the phenyl group at position 2 would act as a spacer which was functionalized at position 4 with an N-acetohydrazide linker that could achieve the key interactions with the essential gate area amino acids. The hydrazide moiety was linked to diverse aryl derivatives to occupy the hydrophobic back pocket of the DFG-out conformation of target kinases. The synthesized quinazolinone derivatives 9a-v demonstrated moderate to potent VEGFR-2 inhibitory activity with IC50 spanning from 0.29 to 5.17 µM. Further evaluation of the most potent derivatives on FGFR-1, BRAFWT and BRAFV600E showed that the quinazolinone N-acetohydrazides 9d, 9e, 9f, 9l and 9m have a potent multi-kinase inhibitory activity. Concurrently, 9b, 9d, 9e, 9k, 9l, 9o, 9q demonstrated potent growth inhibitory activity on NCI cancer cell lines with GI50 reaching 0.72 µM. In addition, compound 9e arrested the cell cycle progression in MDA-MB-231 cell line at the G2/M phase and showed the ability to induce apoptosis.

Piperazine-2-carboxylic acid derivatives as MTDLs anti-Alzheimer agents: Anticholinesterase activity, mechanistic aspect, and molecular modeling studies.

Development of Multitarget-Directed Ligands (MTDLs) is a promising approach to combat the complex etiologies of Alzheimer's disease (AD). Herein we report the design, synthesis, and characterization of a new series of 1,4-bisbenzylpiperazine-2-carboxylic acid derivatives 3-5(a-g), 7a-f, 8a-s, and their piperazine-2-yl-1,3,4-oxadiazole analogs 6a-g. In vitro inhibitory effect against Electrophorus electricus acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) from Equine serum was evaluated using modified Ellman's method, considering donepezil and tacrine as reference drugs. Lineweaver-Burk plot analysis of the results proved competitive inhibition of AChE and BChE with Ki values, in low micromolar range. The free carboxylic acid series 4a-g showed enhanced selectivity for AChE. Hence, 4c, 1,4-bis (4-chlorobenzyl)-piperazinyl-2-carboxylic acid), was the most active member of this series (Ki (AChE) = 10.18 ± 1.00 µM) with clear selectivity for AChE (SI âˆ¼ 17.90). However, the hydroxamic acids 7a-f and carboxamides 8a-s congeners were more potent and selective inhibitors of BChE (SI âˆ¼ 5.38 - 21862.5). Extraordinarily, 1,4-bis (2-chlorobenzyl)-piperazinyl-2-hydroxamic acid 7b showed promising inhibitory activity against BChE enzyme (Ki = 1.6 ± 0.08 nM, SI = 21862.5), that was significantly superior to that elicited by donepezil (Ki = 12.5 ± 2.6 µM) and tacrine (Ki = 17.3 ± 2.3 nM). Cytotoxicity assessment of 4c and 7b, on human neuroblastoma (SH-SY5Y) cell lines, revealed lower toxicity than staurosporine and was nearly comparable to that of donepezil. Molecular docking and molecular dynamics simulation afforded unblemished insights into the structure-activity relationships for AChE and BChE inhibition. The results showed stable binding with fair H-bonding, hydrophobic and/or ionic interactions to the catalytic and peripheral anionic sites of the enzymes. In silico predicted ADME and physicochemical properties of conjugates showed good CNS bioavailability and safety parameters. In this regard, compound (7b) might be considered as a promising inhibitor of BChE with an innovative donepezil-based anti-Alzheimer activity. Further assessments of the most potent AChE and BChE inhibitors as potential MTDLs anti-Alzheimer's agents are under investigation with our research group and will be published later.

Discovery of highly functionalized grayanane diterpenoids from the flowers of Rhododendron molle as potent analgesics.

A systematical investigation on the chemical constituents of the flowers of Rhododendron molle (Ericaceae) led to the isolation and characterization of thirty-eight highly functionalized grayanane diterpenoids (1-38), including twelve novel analogues molleblossomins A-L (1-12). Their structures were elucidated by comprehensive methods, including 1D and 2D NMR analysis, calculated ECD, 13C NMR calculations with DP4+ probability analysis, and single crystal X-ray diffraction. Molleblossomins A (1), B (2), and E (5) are the first representatives of 2ß,3ß:9ß,10ß-diepoxygrayanane, 2,3-epoxygrayan-9(11)-ene, and 5,9-epoxygrayan-1(10),2(3)-diene diterpenoids, respectively. Molleblossomins G (7) and H (8) represent the first examples of 1,3-dioxolane-grayanane conjugates furnished with the acetaldehyde and 4-hydroxylbenzylidene acetal moieties, respectively. All grayanane diterpenoids 1-38 were screened for their analgesic activities in the acetic acid-induced writhing model, and all of them exhibited significant analgesic activities. Diterpenoids 6, 13, 14, 17, 20, and 25 showed more potent analgesic effects than morphine at a lower dose of 0.2 mg/kg, with the inhibition rates of 51.4%, 68.2%, 94.1%, 66.9%, 97.7%, and 60.0%, respectively. More importantly, even at the lowest dose of 0.04 mg/kg, rhodomollein X (14), rhodojaponin VI (20), and rhodojaponin VII (22) still significantly reduced the number of writhes in the acetic acid-induced pain model with the percentages of 61.7%, 85.8%, and 64.6%, respectively. The structure-activity relationship was summarized and might provide some hints to design novel analgesics based on the functionalized grayanane diterpenoids.

Effect of extraction methods on the chemical, structural, and rheological attributes of fructan derived from Arctium lappa L. roots.

The focus of this study was the evaluation of how extraction techniques impact the chemical, structural, and rheological attributes of fructans extracted from Arctium lappa L. roots. Three distinct extraction procedures were used, utilizing water as solvent, infusion extraction conducted at ambient temperature (25 °C for 5 min), thermal extraction employing reflux (100 °C for 2 h), and ultrasound-assisted extraction (50 °C for 1.38 h with a 158 W output). Chemical characterization by Nuclear Magnetic Resonance (NMR) and colorimetric analyses revealed the obtaining of inulin-type fructans (yield 83 %). The degree of polymerization (DP) was found to be the lowest for ultrasound-assisted extraction (14.38), followed by the room-temperature (20.41) and thermal (21.14) extraction techniques. None of the extraction techniques appeared to modify the molecular structure of the isolated compounds. In X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) analyses, distinct crystallization patterns were observed for the room-temperature and thermal extraction techniques, though all fractions consistently exhibited characteristic bands of inulin-type fructan. Rheological assessments indicated a viscoelastic nature of the fractions, with those extracted thermally demonstrating a greater viscosity. This study shows that the choice of extraction method can influence the structural characteristics of inulin-type fructans derived from the burdock root.

Change in thermal stability and molecular structure characteristics of whey protein beta-lactoglobulin upon the interaction with levamisole hydrochloride.

The interaction between beta-lactoglobulin (BLG) and anthelmintic compounds including levamisole (LEV) is a matter of great concern as it not only poses potential health and environmental risks but also has significant implications for food processing and production. The mechanisms of LEV-BLG interaction were investigated through spectral and molecular modeling approaches. Fluorescence and UV-Visible investigations indicated the formation of a spontaneous and stable LEV-BLG complex. Structural changes of BLG were revealed by circular dichroism and Fourier transform infrared studies. The thermal stability of BLG increased in the presence of LEV. Molecular docking studies indicated the best mode of LEV-BLG interaction and molecular dynamics simulation confirmed the stability of the LEV-BLG complex. In conclusion, our study sheds light on the potential of BLG to interact with deleterious substances such as anthelmintic agents, thus highlighting the necessity of further research in this field to assure food safety and prevent any health hazards.

Starch molecular structures in relation to properties of ratoon rice produced by different ratooning practices.

The development of forage-grain ratoon rice (RR) pattern could ensure food security and promote silage production. Herein three indica rice varieties were used to investigate the influence of different forage clipping stages (heading, milk-ripe, wax-ripe, and full-ripe) on starch molecular structures and RR properties. The apparent amylose contents (AAC) of starches increased, but pasting viscosities, gelatinization temperatures and starch sizes decreased with the postponement of clipping stages due to the retardation of endosperm development. The starches showed A-type crystalline structure with increased in vitro digestibility; however relative crystallinity decreased by 13.45 % to 23.89 %. The short fa (DP 6-12) chains of amylopectin increased while long fb3 (DP ≥ 37) chains decreased (p < 0.05). The proportions of amylose chains with DP 100-2000 increased but those with DP 2000-20,000 decreased. Rice grain strength was positively correlated with fb3 chains while negatively correlated with fa chain. The hardness of cooked RR was positively correlated with AAC while negatively correlated with fb2 (DP 25-36). RR clipping at milk-ripe stage had the highest grain strength and moderate texture properties. The elucidation of structure-property relationships is helpful for RR utilization and development of suitable cultivation conditions for RR production.

New pyrazolyl-thiazolidinone/thiazole derivatives as celecoxib/dasatinib analogues with selective COX-2, HER-2 and EGFR inhibitory effects: design, synthesis, anti-inflammatory/anti-proliferative activities, apoptosis, molecular modelling and ADME studies.

Two new series of pyrazolyl-thiazolidinone/thiazole derivatives 16a-b and 18a-j were synthesised, merging the scaffolds of celecoxib and dasatinib. Compounds 16a, 16b and 18f inhibit COX-2 with S.I. 134.6, 26.08 and 42.13 respectively (celecoxib S.I. = 24.09). Compounds 16a, 16b, 18c, 18d and 18f inhibit MCF-7 with IC50 = 0.73-6.25 µM (dasatinib IC50 = 7.99 µM) and (doxorubicin IC50 = 3.1 µM) and inhibit A549 with IC50 = 1.64-14.3 µM (dasatinib IC50 = 11.8 µM and doxorubicin IC50 = 2.42 µM) with S.I. (F180/MCF7) of 33.15, 7.13, 18.72, 13.25 and 8.28 respectively higher than dasatinib (4.03) and doxorubicin (3.02) and S.I. (F180/A549) of 14.75, 12.96, 4.16, 7.07 and 18.88 respectively higher than that of dasatinib (S.I. = 2.72) and doxorubicin (S.I = 3.88). Derivatives 16a, 18c, 18d, 18f inhibit EGFR and HER-2 IC50 for EGFR of 0.043, 0.226, 0.388, 0.19 µM respectively and for HER-2 of 0.032, 0.144, 0.195, 0.201 µM respectively.

New spiro-indeno[1,2-b]quinoxalines clubbed with benzimidazole scaffold as CDK2 inhibitors for halting non-small cell lung cancer; stereoselective synthesis, molecular dynamics and structural insights.

Despite the crucial role of CDK2 in tumorigenesis, few inhibitors reached clinical trials for managing lung cancer, the leading cause of cancer death. Herein, we report combinatorial stereoselective synthesis of rationally designed spiroindeno[1,2-b]quinoxaline-based CDK2 inhibitors for NSCLC therapy. The design relied on merging pharmacophoric motifs and biomimetic scaffold hopping into this privileged skeleton via cost-effective one-pot multicomponent [3 + 2] cycloaddition reaction. Absolute configuration was assigned by single crystal x-ray diffraction analysis and reaction mechanism was studied by Molecular Electron Density Theory. Initial MTT screening of the series against A549 cells and normal lung fibroblasts Wi-38 elected 6b as the study hit regarding potency (IC50 = 54 nM) and safety (SI = 6.64). In vitro CDK2 inhibition assay revealed that 6b (IC50 = 177 nM) was comparable to roscovitine (IC50 = 141 nM). Docking and molecular dynamic simulations suggested that 6b was stabilised into CDK2 cavity by hydrophobic interactions with key aminoacids.

Design, synthesis, and biological activity studies of carbonic anhydrase inhibitors.

Carbonic anhydrase (CA) enzymes are a common catalytic enzyme in many organisms. Vertebrates and invertebrates have different CA isoforms. Sixteen different isozymes of the α-CA isoform found in vertebrates have been identified so far. The main task of this enzyme is to catalyze the reversible conversion of carbon dioxide into bicarbonate and hydrogen ions in the body. It is widely distributed in many organs and tissues. They are involved in important physiological processes such as pH and CO2 homeostasis, biosynthetic reactions such as gluconeogenesis, lipogenesis, ureagenesis, bone resorption, calcification, tumorigenicity, and electrolyte secretion. As a result of the literature research, it has been determined that the most effective inhibitor of the carbonic anhydrase enzyme is sulfonamides. The R group in the general molecular structure of R-SO2-NH2 generally consists of aromatic or heteroaromatic ring systems. The sulfonamides interact strongly with the Zn2+ ions in the active site of the enzyme. In this study, 10 sulfonamide derivatives were synthesized. Analyses of the obtained compounds are evaluated by using 1H NMR, 13C NMR and HRMS spectroscopic methods. The inhibition effect of the obtained compounds on the carbonic anhydrase enzyme was investigated by means of in vitro kit method. For the selected compounds, docking studies were performed and the enzyme active sites and binding points were determined. It was revealed that the strongest interaction with CA enzymes (CA-I, CA-II, CA-IX, CA-XII) active sites was observed with the compound 2e.

Indole-pyridine carbonitriles: multicomponent reaction synthesis and bio-evaluation as potential hits against diabetes mellitus.

Background: Diabetes mellitus is a significant health disorder; therefore, researchers should focus on discovering new drug candidates. Methods: A series of indole-pyridine carbonitrile derivatives, 1-34, were synthesized through a one-pot multicomponent reaction and evaluated for antidiabetic and antioxidant potential. Results: In this library, 12 derivatives - 1, 2, 4, 5, 7, 8, 10-12, 14, 15 and 31 - exhibited potent inhibitory activities against α-glucosidase and α-amylase enzymes, in comparison to acarbose (IC50 = 14.50 ± 0.11 µM). Furthermore, kinetics, absorption, distribution, metabolism, excretion and toxicity and molecular docking studies were used to interpret the type of inhibition, binding energies and interactions of ligands with target enzymes. Conclusion: These results indicate that the compounds may be promising hits for controlling diabetes mellitus and its related complications.

Arthproliferins A-D, Four New Sesterterpenes from the Mangrove-Sediment-Derived Fungus Arthrinium sp. SCSIO41221.

Four new sesterterpenes, arthproliferins A-D (1-4), together with four known derivatives, were isolated and characterized from the mangrove-sediment-derived fungus Arthrinium sp. SCSIO41221. Their structures were determined using detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses. Some of the isolated compounds were evaluated for their cytotoxicity in vitro. The results revealed that terpestacin (6) exhibited significant activity with an IC50 value of 20.3 µM, and compounds 2 and 5 were found to show weak inhibitory effects against U87MG-derived GSCs.

New Thiazolyl-Pyrazoline Derivatives as Potential Dual EGFR/HER2 Inhibitors: Design, Synthesis, Anticancer Activity Evaluation and In Silico Study.

A new series of thiazolyl-pyrazoline derivatives (4a-d, 5a-d 6a, b, 7a-d, 8a, b, and 10a, b) have been designed and synthesized through the combination of thiazole and pyrazoline moieties, starting from the key building blocks pyrazoline carbothioamides (1a-b). These eighteen derivatives have been designed as anticipated EGFR/HER2 dual inhibitors. The efficacy of the developed compounds in inhibiting cell proliferation was assessed using the breast cancer MCF-7 cell line. Among the new synthesized thiazolyl-pyrazolines, compounds 6a, 6b, 10a, and 10b displayed potent anticancer activity toward MCF-7 with IC50 = 4.08, 5.64, 3.37, and 3.54 µM, respectively, when compared with lapatinib (IC50 = 5.88 µM). In addition, enzymatic assays were also run for the most cytotoxic compounds (6a and 6b) toward EGFR and HER2 to demonstrate their dual inhibitory activity. They revealed promising inhibition potency against EGFR with IC50 = 0.024, and 0.005 µM, respectively, whereas their IC50 = 0.047 and 0.022 µM toward HER2, respectively, compared with lapatinib (IC50 = 0.007 and 0.018 µM). Both compounds 6a and 10a induced apoptosis by arresting the cell cycle of the MCF-7 cell line at the G1 and G1/S phases, respectively. Molecular modeling studies for the promising candidates 6a and 10a showed that they formed the essential binding with the crucial amino acids for EGFR and HER2 inhibition, supporting the in vitro assay results. Furthermore, ADMET study predictions were carried out for the compounds in the study.

Neurite Outgrowth-Inducing Drimane-Type Sesquiterpenoids Isolated from Cultures of the Polypore Abundisporus violaceus MUCL 56355.

Abundisporin A (1), together with seven previously undescribed drimane sesquiterpenes named abundisporins B-H (2-8), were isolated from a polypore, Abundisporus violaceus MUCL 56355 (Polyporaceae), collected in Kenya. Chemical structures of the isolated compounds were elucidated based on exhaustive 1D and 2D NMR spectroscopic measurements and supported by HRESIMS data. The absolute configurations of the isolated compounds were determined by using Mosher's method for 1-4 and TDDFT-ECD calculations for 4 and 5-8. None of the isolated compounds exhibited significant activities in either antimicrobial or cytotoxicity assays. Notably, all of the tested compounds demonstrated neurotrophic effects, with 1 and 6 significantly increasing outgrowth of neurites when treated with 5 ng/mL NGF.

ent-Clavilactone J and Its Quinone Derivative, Meroterpenoids from the Fungus Resupinatus sp.

Metabolites 1 and 2, isolated from cultures of the basidiomycete Resupinatus sp. BCC84615, collected in a tropical forest in northeastern Thailand, showed weak antibiotic activity against Bacillus subtilis and Staphylococcus aureus and cytotoxicity against cancer cell lines. Their planar structures were elucidated by high-resolution electrospray ionization mass spectrometry and NMR spectroscopy as clavilactone J, known from the basidiomycete Ampulloclitocybe clavipes, and its new 1,4-benzoquinone derivative. A detailed analysis of the ROESY correlations in 1 confirmed the recent revision of the relative configuration of clavilactone J. However, specific rotation and Cotton effects observed by electronic circular dichroism were contrary to those of the clavilactones; thus, we assigned a rare antipodal absolute configuration.