Search Results (10)

The escalating threat of antibiotic-resistant bacteria and fungi underscores an urgent need for new antimicrobial agents. This study aimed to synthesize and evaluate the antimicrobial activities of two series of 3-alkylidene-2-indolone derivatives. We synthesized 32 target compounds, among which 25 exhibited moderate to high antibacterial or antifungal activities. Notably, compounds 10f, 10g, and 10h demonstrated the highest antibacterial activity with a minimum inhibitory concentration (MIC) of 0.5 μg/mL, matching the activity of the positive control gatifloxacin against three Gram-positive bacterial strains: Staphylococcus aureus ATCC 6538, 4220, and Methicillin-resistant Staphylococcus aureus ATCC 43300. Moreover, the three most active compounds 10f, 10g, and 10h were evaluated for their in vitro cytotoxicity in the HepG2 cancer cell line and L-02; only compound 10h was found to exert some level of cytotoxicity. These findings suggest that the synthesized 3-alkylidene-2-indolone derivatives hold potential for further development as antibacterial agents. Full article

Garcinia gummi-gutta, commonly known as Garcinia cambogia (syn.), is a popular traditional herbal medicine known for its role in treating obesity, and has been incorporated into several nutraceuticals globally for this purpose. The fruit rind is also used as a food preservative and a condiment because of its high content of hydroxycitric acid, which imparts a sharp, sour flavour. This review highlights the major bioactive compounds present in the tree Garcinia gummi-gutta, with particular emphasis on (2S, 3S)-tetrahydro-3-hydroxy-5-oxo-2,3-furan dicarboxylic acid, commonly referred to as garcinia acid. This acid can be isolated in large amounts through a simple procedure. Additionally, it explores the synthetic transformations of garcinia acid into biologically potent and functionally useful enantiopure compounds, a relatively under-documented area in the literature. This acid, with its six-carbon skeleton, a γ-butyrolactone moiety, and two chiral centres bearing chemically amenable functional groups, offers a versatile framework as a chiron for the construction of diverse molecules of both natural and synthetic origin. The synthesis of chiral 3-substituted and 3,4-disubstituted pyrrolidine-2,5-diones, analogues of the Quararibea metabolite—a chiral enolic-γ-lactone; the concave bislactone skeletons of fungal metabolites (+)-avenaciolide and (−)-canadensolide; the structural skeletons of the furo[2,3-b]furanol part of the anti-HIV drug Darunavir; (−)-tetrahydropyrrolo[2,1-a]isoquinolinones, an analogue of (−)-crispine A; (−)-hexahydroindolizino[8,7-b]indolones, an analogue of the naturally occurring (−)-harmicine; and furo[2,3-b]pyrroles are presented here. Full article

Pyrano [3,4-b]indol-1(9H)-ones and indolo [2,3-c]coumarins are important classes of heterocyclic compounds with versatile biological activities. Herein, we describe a straightforward and scalable synthesis of 3,6-dihydro-5H-pyrazolo [4′,3′:5,6]pyrano [3,4-b]indol-5-one, a pyrazolo-fused pyrano [3,4-b]indolone, via a three step approach including Fischer-indole synthesis and intramolecular esterification. The compound is fully characterized by means of ¹H and ¹³C NMR spectra, using direct and long-range heteronuclear correlation experiments (HMBC and HMQC). Full article

A series of novel indolone derivatives were synthesized and evaluated for their binding affinities toward MDM2 and MDMX. Some compounds showed potent MDM2 and moderate MDMX activities. Among them, compound A13 exhibited the most potent affinity toward MDM2 and MDMX, with a K_i of 0.031 and 7.24 μM, respectively. A13 was also the most potent agent against HCT116, MCF7, and A549, with IC₅₀ values of 6.17, 11.21, and 12.49 μM, respectively. Western blot analysis confirmed that A13 upregulated the expression of MDM2, MDMX, and p53 by Western blot analysis. These results indicate that A13 is a potent dual p53-MDM2 and p53-MDMX inhibitor and deserves further investigation. Full article

Five new alkaloids have been isolated from the lipophilic extract of the Antarctic tunicate Synoicum sp. Deep-sea specimens of Synoicum sp. were collected during a 2011 cruise of the R/V Nathanial B. Palmer to the southern Scotia Arc, Antarctica. Crude extracts from the invertebrates obtained during the cruise were screened in a zebrafish-based phenotypic assay. The Synoicum sp. extract induced embryonic dysmorphology characterized by axis truncation, leading to the isolation of aminopyrimidine substituted indolone (1–4) and indole (5–12) alkaloids. While the primary bioactivity tracked with previously reported meridianins A–G (5–11), further investigation resulted in the isolation and characterization of australindolones A–D (1–4) and the previously unreported meridianin H (12). Full article

This review focuses on the synthesis of polyheterocyclic structures with a variety of medicinal and optoelectronic applications, starting from readily available 4,5,6,7-tetrahydroindol-4-one analogs. First, routes toward the 4,5,6,7-tetrahydroindol-4-one starting materials are summarized, followed by synthetic pathways towards polyheterocyclic structures which are categorized based on the size and attachment point of the newly formed (hetero)cyclic ring. Full article

Dunnione, a natural product isolated from the leaves of Streptocarpus dunnii (Gesneriaceae), acts as a substrate for quinone-reductases that may be associated with its antimalarial properties. Following our exploration of reactive oxygen species-producing compounds such as indolones, as possible new approaches for the research of new ways to treat this parasitosis, we explored derivatives of this natural product and their possible antiplasmodial and antimalarial properties, in vitro and in vivo, respectively. Apart from one compound, all the products tested had weak to moderate antiplasmodial activities, the best IC₅₀ value being equal to 0.58 µM. In vivo activities in the murine model were moderate (at a dose of 50 mg/kg/mice, five times higher than the dose of chloroquine). These results encourage further pharmacomodulation steps to improve the targeting of the parasitized red blood cells and antimalarial activities. Full article

The present work describes the synthesis of a new copper (II) complex with bidentate ligands based on oxindole (indolin-2-one) derivatives, namely: 1H,1′H,1″H-[2,3′:2′,3″-terbenzo[b]pyrrol]-2″(3″H)-one (L1) and [sodium diethyldithiocarbamate (DTC)] (L2) as a second bidentate ligand. The ligand L1 was prepared by the cyclization reaction of oxindole (2-indolone) with phosphorus oxychloride. A mixed-ligand was synthesized using L1 and L2 ligands with copper (Cu (II)) via a simple reflux process. The synthesized mixed Cu (II) complex [C₅₃H₄₄CuN₇O₄S₂ and [Cu(L1)₂(L2)]2H₂O] exhibited superior solubility in organic solvents like dichloromethane, chloroform, ethanol, methanol, DMF and DMSO. The optical characterizations revealed that the synthesized Cu (II) complex displayed a broad band (²E_g→²T_2g) with the absorption at ~420 nm, suggesting a distorted octahedral geometry due to the strong Jahn-Teller distortion of the Cu²⁺ ion. The elemental analysis confirmed the existence of Cu, C, S, N, and other elements in the synthesized mixed Cu (II) complex. The physicochemical studies of the organic ligand and Cu(II) complex were investigated by TG analysis, NMR, FTIR, SEM, EDX, electronic spectra and cyclic voltammetry measurements. The detection of chloride ions with the prepared mixed Cu(II) complex was studied by cyclic voltammetry measurements at different scan rates. Full article

Vibrio diabolicus A1SM3 strain was isolated from a sediment sample from Manaure Solar Saltern in La Guajira and the produced crude extracts have shown antibacterial activity against methicillin-resistant Staphylococcus aureus and cytotoxic activity against human lung cell line. Thus, the aim of this research was to identify the main compound responsible for the biological activity observed and to systematically study how each carbon and nitrogen source in the growth media, and variation of the salinity, affect its production. For the characterization of the bioactive metabolites, 15 fractions obtained from Vibrio diabolicus A1SM3 crude extract were analyzed by HPLC-MS/MS and their activity was established. The bioactive fractions were dereplicated with Antibase and Marinlit databases, which combined with nuclear magnetic resonance (NMR) spectra and fragmentation by MS/MS, led to the identification of 2,2-di(3-indolyl)-3-indolone (isotrisindoline), an indole-derivative antibiotic, previously isolated from marine organisms. The influence of the variations of the culture media in isotrisindoline production was established by molecular network and MZmine showing that the media containing starch and peptone at 7% NaCl was the best culture media to produce it. Also, polyhydroxybutyrates (PHB) identification was established by MS/MS mainly in casamino acids media, contributing to the first report on PHB production by this strain. Full article

Indolone-N-oxides have antiplasmodial properties against Plasmodium falciparum at the erythrocytic stage, with IC50 values in the nanomolar range. The mechanism of action of indolone derivatives involves the production of free radicals, which follows their bioreduction by an unknown mechanism. In this study, we hypothesized that human quinone reductase 2 (hQR2), known to act as a flavin redox switch upon binding to the broadly used antimalarial chloroquine, could be involved in the activity of the redox-active indolone derivatives. Therefore, we investigated the role of hQR2 in the reduction of indolone derivatives. We analyzed the interaction between hQR2 and several indolone-type derivatives by examining enzymatic kinetics, the substrate/protein complex structure with X-ray diffraction analysis, and the production of free radicals with electron paramagnetic resonance. The reduction of each compound in cells overexpressing hQR2 was compared to its reduction in naïve cells. This process could be inhibited by the specific hQR2 inhibitor, S29434. These results confirmed that the anti-malarial activity of indolone-type derivatives was linked to their ability to serve as hQR2 substrates and not as hQR2 inhibitors as reported for chloroquine, leading to the possibility that substrate of hQR2 could be considered as a new avenue for the design of new antimalarial compounds. Full article