Phytopathogenic fungi cause plant diseases and economic losses in agriculture. To efficiently control plant pathogen infections, a total of 19 spirotryprostatin A derivatives and 26 spirooxindole derivatives were designed, synthesized, and tested for their antifungal activity against ten plant pathogens. Additionally, the intermediates of spirooxindole derivatives were investigated, including proposing a mechanism for diastereoselectivity and performing amplification experiments. The bioassay results demonstrated that spirotryprostatin A derivatives possess good and broad-spectrum antifungal activities. Compound 4d exhibited excellent antifungal activity in vitro, equal to or higher than the positive control ketoconazole, against Helminthosporium maydis, Trichothecium roseum, Botrytis cinerea, Colletotrichum gloeosporioides, Fusarium graminearum, Alternaria brassicae, Alternaria alternate, and Fusarium solan (MICs: 8-32 µg/mL). Compound 4k also displayed remarkable antifungal activity against eight other phytopathogenic fungi, including Fusarium oxysporium f. sp. niveum and Mycosphaerella melonis (MICs: 8-32 µg/mL). The preliminary structure-activity relationships (SARs) were further discussed. Moreover, molecular docking studies revealed that spirotryprostatin A derivatives anchored in the binding site of succinate dehydrogenase (SDH). Therefore, these compounds showed potential as natural compound-based chiral fungicides and hold promise as candidates for further enhancements in terms of structure and properties.

UNASSIGNED: The present study investigates the potential bioactivity of twelve experimentally designed C-2 quaternary indolinones against Providencia spp., a bacterial group of the Enterobacteriaceae family known to cause urinary tract infections. The study aims to provide insights into the bioactive properties of the investigated compounds and their potential use in developing novel treatments against Providencia spp. The experimental design of indolinones, combined with their unique chemical structure, makes them attractive candidates for further investigation. The results of this research may contribute to the development of novel therapeutic agents to combat Providencia spp. infections.
UNASSIGNED: The synthesized indolinones (moL1-moL12) are evaluated to identify any superior activity, particularly focusing on moL12, which possesses aza functionality. The antimicrobial activities of all twelve compounds are tested in triplicates against six different Gram-positive and Gram-negative organisms, including P. vermicola (P<0.05). Computational methods have been employed to assess the pharmacokinetic properties of the compounds.
UNASSIGNED: Among the synthesized indolinones, moL12 exhibits superior activity compared to the other compounds with similar skeleton but different functional moieties. All six strains tested, including P. vermicola, demonstrated sensitivity to moL12. Computational studies support the pharmacokinetic properties of moL12, indicating acceptable absorption, distribution, metabolism, excretion, and toxicity characteristics.
UNASSIGNED: Utilizing the PPI approach, we have identified a promising target, FabD, in Gram-negative bacteria. Our analysis has shown that moL12 exhibits significant potential in binding with FabD, thereby, might inhibit cell wall formation, and display superior antimicrobial activity compared to other compounds. Consequently, moL12 may be a potential therapeutic agent that could be used to combat urinary tract infections caused by Providencia spp. The findings of this research hold significant promise for the development of new and effective treatments for bacterial infections.

A series of 16 novel spirooxindole analogs 8a-p were designed and constructed via cost-effective single-step multicomponent [3+2] cycloaddition reaction of azomethine ylide (AY) generated in situ from substituted isatin (6a-d) with suitable amino acids (7a-c) and ethylene-engrafted pyrazole derivatives (5a,b). The potency of all compounds was assayed against a human breast cancer cell line (MCF-7) and a human liver cell line (HepG2). Spiro compound 8c was the most active member among the synthesized candidates, with exceptional cytotoxicity against the MCF-7 and HepG2 cell lines, with IC50 values of 0.189 ± 0.01 and 1.04 ± 0.21 µM, respectively. The candidate 8c exhibited more potent activity (10.10- and 2.27-fold) than the standard drug roscovitine (IC50  = 1.91 ± 0.17 µM (MCF-7) and 2.36 ± 0.21 µM (HepG2)). Compound 8c was investigated for epidermal growth factor receptor (EGFR) inhibition; it exhibited promising IC50 values of 96.6 nM compared with 67.3 nM for erlotinib. The IC50 value of 8c (34.98 nM) exhibited cyclin-dependent kinase 2 (CDK-2) inhibition, being more active than roscovitine the (IC50  = 140 nM) in targeting the CDK-2 kinase enzyme. Additionally, for apoptosis induction of compound 8c in MCF-7, it upregulated the expression levels of proapoptotic genes for P53, Bax, caspases-3, 8, and 9 at up to 6.18, 4.8, 9.8, 4.6, 11.3 fold-change, respectively, and downregualted the level of the antiapoptotic gene for Bcl-2 by 0.14-fold. Finally, a molecular docking study of the most active compound 8c highlighted a good binding affinity with Lys89 as the key amino acid for CDK-2 inhibition.

In this study we have performed the in vitro anticancer activity of spiro oxindole derivatives against MCF-7 (human Adreno carcinoma) and MDA-MB-231 (triple negative breast cancer) cell lines to propose a possible role of these derivatives in the treatment of cancer. Compound 6, which has an N-benzyl substitution with a chloro group on the indolin-2-one scaffold, had the most potent activity against MCF-7 (3.55 ± 0.49 μM) and MDA-MB-231 (4.40 ± 0.468 μM) of all the synthesized molecules. A normal mouse embryonic fibroblast (NIH/3 T3) cell line was used to test the cellular toxicity of these derivatives. The results showed that none of the compounds were cytotoxic to normal cells. In addition, pharmacokinetic (ADME) and toxicity study profiles were predicted in silico. All the synthesized derivatives (1 to 7) demonstrated the necessary physicochemical properties for bioavailability. Finally, in vitro results of promising compound 6 were validated using molecular docking and dynamic simulation studies, which revealed their binding affinities and conformational stability in the binding cavity. Thus, these derivatives may serve as lead structures for a new generation of anticancer agents.

The aggregation process of α-synuclein (α-syn) is substantial in the pathogenesis of Parkinson\'s disease. Indolinone derivatives are inhibitors of α-syn aggregates and can be used as PET-based radiotracers for imaging α-syn fibrils. However, no investigations on the metabolism of indolinone derivatives have been reported until now. In the present research, a 13C and 15N isotope labeling strategy was developed to synthesize compound [13C2,15N]-(Z)-1-(4-aminobenzyl)-3-((E)-(3-phenyl)allylidene)indolin-2-one (M0\'), which was then used in a study of metabolism in hepatocytes. The metabolites were characterized using accurate mass and characteristic ion measurements. In the metabolic system, compound M0\' was the main component (accounting for 97.5% of compound-related components) after incubation in hepatocytes for 3 h, which indicated that compound M0\' possessed great metabolic stability. Seven metabolites have been successfully verified by UPLC/Q TOF MS in metabolic studies, including hydroxyl M0\' (M1\'), hydroxyl and methylated M0\' (M2\'), N-acetylated M0\' (M3\'), sulfate of hydroxyl M0\' (M4\'), the glucose conjugate of M0\' (M5\'), glucuronide conjugate of M0\' (M6\'), and glucuronide conjugate of hydroxyl M0\' (M7\'). The study on metabolism provides the important information to develop effective α-syn aggregate inhibitors and new PET-tracer-related indolinone derivatives.

OBJECTIVE: Presently, the pandemic of COVID-19 has worsened the situation worldwide and received global attention. The United States of America have the highest numbers of a patient infected by this disease followed by Brazil, Russia, India and many other countries. Moreover, lots of research is going on to find out effective vaccines or medicine, but still, no potent vaccine or drug is discovered to cure COVID-19. As a consequence, many types of research have designated that computer-based studies, such as protein-ligand interactions, structural dynamics, and chembio modeling are the finest choice due to its low cost and time-saving features. Here, oxindole derivatives have been chosen for docking because of their immense pharmacological applications like antiviral, antidiabetic, anti-inflammatory, and so on. Molecular docking of 30 oxindole derivatives done on the crystallized structure of the protein (COVID-19 Mpro).
METHODS: The process of docking, interaction, and binding the structure of ligand with protein has executed using Molegro Virtual Docker v.7.0.0 (MVD) and visualized the usage by Molegro Molecular Viewer v.7.0.0 (MMV).
RESULTS: Among the 30 derivatives, the outcomes depicted better steric interaction and hydrogen bonding amongst OD-22 ligand, OD-16 ligand, OD-4 ligand, and OD-9 ligand (oxindole derivatives) with COVID-19. In addition to this, the comparative study of these four compounds with existing drugs that are under clinical trials shows comparatively good results in terms of its MolDock scores, H-bonding and steric interactions.
CONCLUSIONS: Hence, It is proposed that these four oxindole derivatives have good potential as a new drug against coronavirus as possible therapeutic agents.

In a sustained search for novel α-amylase inhibitors for the treatment of type 2 diabetes mellitus (T2DM), we report herein the synthesis of a series of nineteen novel rhodanine-fused spiro[pyrrolidine-2,3\'-oxindoles]. They were obtained by one-pot three component [3 + 2] cycloaddition of stabilized azomethine ylides, generated in situ by condensation of glycine methyl ester and the cyclic ketones 1H-indole-2,3-dione (isatin), with (Z)-5-arylidine-2-thioxothiazolidin-4-ones. The highlight of this protocol is the efficient high-yield construction of structurally diverse rhodanine-fused spiro[pyrrolidine-2,3\'-oxindoles] scaffolds, including four contiguous stereocenters, along with excellent regio- and diastereoselectivities. The stereochemistry of all compounds was confirmed by NMR and corroborated by an X-ray diffraction study performed on one derivative. All cycloadducts were evaluated in vitro for their α-amylase inhibitory activity and showed good α-amylase inhibition with IC50 values ranging between 1.49 ± 0.10 and 3.06 ± 0.17 µM, with respect to the control drug acarbose (IC50 = 1.56 µM). Structural activity relationships (SARs) were also established for all synthesized compounds and the binding interactions of the most active spiropyrrolidine derivatives were modelledby means of molecular insilico docking studies. The most potent compounds 5 g, 5 k, 5 s and 5 l were further screened in vivo for their hypoglycemic activity in alloxan-induced diabetic rats, showing a reduction of the blood glucose level. Therefore, these spiropyrrolidine derivatives may be considered as promising candidates for the development of new classes of antidiabetic drugs.

The our previous study synthesized the chrysin-chromene-spirooxindole hybrids 3, and further found compound 3e had good antitumor activity against A549 cells in vitro through multi-target co-regulation of the p53 signalling pathway to inhibit the proliferation of A549 cells. This study was designed to evaluate the antitumor effects of compound 3e on Lewis lung carcinoma of C57BL/6 mice in vivo. Compound 3e significantly inhibited the growth of transplanted tumors in C57BL/6 mice and induced the apoptosis of tumor cells. Further studies showed that compound 3e activates and expands the anti-cancer activity of p53 by inhibiting the expression of MDM2, Akt and 5-Lox proteins, accordingly promotes the expressions Bax and inhibit the Bcl-2 protein, the release of Cyt c as well, which resulted in the activation of apoptotic pathway in tumor cells eventually. Moreover, Compound 3e inhibited tumor metastasis by down-regulating VEGF, ICAM-1 and MMP-2 protein expression and angiogenesis. These results suggested that compound 3e exerts an effective antitumor activity in vivo through activating the p53 signaling pathway, which could be exploited as a promising candidate for the development of new anti-tumour drugs.

OBJECTIVE: Alzheimer\'s disease (AD) is a growing concern in the modern society. The current drugs approved by FDA are not very promising. Rhynchophylline (RIN) is a major active tetracyclic oxindole alkaloid stem from traditional Chinese medicine uncaria species, which has potential activities beneficial for the treatment of AD. However, the application of rhynchophylline for AD treatment is restricted by the low water solubility, low concentration in brain tissue and low bioavailability. And there is no study of brain-targeting therapy with RIN. In this work, we prepared rhynchophylline loaded methoxy poly (ethylene glycol)-poly (dl-lactide-co-glycolic acid) (mPEG-PLGA) nanoparticles (NPS-RIN), which coupled with Tween 80 (T80) further for brain targeting delivery (T80-NPS-RIN).
METHODS: Preparation and characterization of T80-NPS-RIN were followed by the detection of transportation across the blood-brain barrier (BBB) model in vitro, biodistribution and neuroprotective effects of nanoparticles.
RESULTS: The results indicated T80-NPS-RIN could usefully assist RIN to pass through the BBB to the brain. T80-NPS-RIN treatment regulated the activity of neurons in vitro.
CONCLUSIONS: The presented data confirmed that rhynchophylline encapsulated mPEG-PLGA nanoparticles coated with Tween 80 could across through the BBB and exhibited efficient neuroprotective effects. The T80-NPS-RIN nanoparticles have a chance to be an alternative drug to the therapy of AD.

Density functional theory is one of the most popular accepted computational quantum mechanical techniques used in the analysis of molecular structure and vibrational spectra. Experimental and theoretical investigations of the molecular structure, electronic and vibrational characteristics of 4-[2-(Dipropylamino) ethyl]-1,3-dihydro-2H-indol-2-one are presented in this work. The title compound was characterized using FT-IR, FT-Raman and UV-Vis spectroscopic techniques. The results were compared with the theoretical calculations obtained using DFT/B3LYP with 6-311++G(d,p) as basis sets and was found to be in good agreement. The complete optimization of the molecular geometry of the title compound was carried out. Further, the vibrational assignments and calculation of potential energy distribution (PED) were reported. NLO has emerged as a key factor in recent researches. Materials showing nonlinear optical properties form the basis of nonlinear optics and development of such materials plays an important role in the present scenario. The current work provides sufficient justification for the title compound to be selected as a good non-linear optical (NLO) candidate. The electronic properties were reported using TD-DFT approach. The HOMO (EHOMO = -5.96 eV), LUMO (ELUMO = -0.80 eV) energies, energy gap and electrophilicity (2.22) was calculated in order to understand the stability, reactivity and bioactivity of the compound under investigation. To comprehend the bonding interactions we have performed the total (TDOS), partial (PDOS) and overlap population or COOP (Crystal Orbital Overlap Population) density of states. The drug likeness values were analyzed to evaluate the potential of the title compound to be an active pharmaceutical component. As a positive proof the paper further explains the molecular docking studies of the said compound. In addition, the stereochemistry of the protein structure was checked using Ramachandran plot. The title compound is a directly acting dopamine D2 agonist. In order to establish relationship between molecular descriptors of compound and its biological activity, QSAR studies have been done within the framework of DFT for 10 dopamine agonist including the title compound. Hence, the research exploration provides requisite information pertaining to the geometry, stability, reactivity and bioactivity of the compound through spectroscopic and quantum chemical methods.