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To explore new compounds with antitumour activity, fifteen phenolic nor-tripterpenes isolated from Celastraceae species, Maytenus jelskii, Maytenus cuzcoina, and Celastrus vulcanicola, have been studied. Their chemical structures were elucidated through spectroscopic and spectrometric techniques, resulting in the identification of three novel chemical compounds. Evaluation on human tumour cell lines (A549 and SW1573, non-small cell lung; HBL-100 and T-47D, breast; HeLa, cervix, and WiDr, colon) revealed that three compounds, named 6-oxo-pristimerol, demethyl-zeylasteral, and zeylasteral, exhibited significant activity (GI50 ranging from 0.45 to 8.6 µM) on at least five of the cell lines tested. Continuous live cell imaging identified apoptosis as the mode of action of selective cell killing in HeLa cells. Furthermore, their effect on a drug-sensitive Saccharomyces cerevisiae strain has been investigated to deepen on their mechanism of action. In dose-response growth curves, zeylasteral and 7α-hydroxy-blepharodol were markedly active. Additionally, halo assays were conducted to assess the involvement of oxidative stress and/or mitochondrial function in the anticancer profile, ruling out these modes of action for the active compounds. Finally, we also delve into the structure-activity relationship, providing insights into how the molecular structure of these compounds influences their biological activity. This comprehensive analysis enhances our understanding of the therapeutic potential of this triterpene type and underscores its relevance for further research in this field. [ABSTRACT FROM AUTHOR]

Complexes [{RuCp(PPh3)2-μ-dmoPTA-1κP:2κ2-N,N′-CuCl}2-μ-Cl-μ-OCH3](CF3SO3)2·(CH3OH)4 (1) and [{RuCp(PPh3)2-μ-dmoPTA-1κP:2κ2-N,N′-NiCl}2-μ-Cl-μ-OH](CF3SO3)2 (2) have been synthesized and characterized. Their antiproliferative activities were assessed against six human solid tumours showing nanomolar GI50 values. The effects of 1 and 2 on SW1573 cells colony formation, HeLa cells action mechanism and their interaction with the pBR322 DNA plasmid were evaluated. [ABSTRACT FROM AUTHOR]

An amide bond is one of the most important functional motifs in chemistry and biology due to its presence in countless biological structures and is of significant synthetic interest. Small-molecule amides are remarkable scaffolds for designing new drugs. Here, we report a new Ugi4CR approach using 5-amino-3,3-protected-oxindole derivatives, carboxylic acids (and nitrophenols), aldehydes (and ketones) and isocyanides to create a library of Ugi-derived isatin-peptoids in moderate to excellent yields, in a one-step, clean, and fast sustainable reaction process. The library was tested against human solid tumor cell lines. The results allowed some preliminary structure–activity relationships to be established. The most active derivative showed GI50 values in the range of 0.06–2.3 μM. [ABSTRACT FROM AUTHOR]

A series of triazole linked tetrahydropyran–oxazole hybrids was synthesized based on a previously reported lead compound with selective antiproliferative activity against human tumour cell lines. The series was prepared to evaluate the impact of LogP and different modifications in the activity, and the new compounds were assayed against A549, HBL‐100, HeLa, SW1573, T‐47D, and WiDr cell lines. Also, the potentiality to be P‐gp substrate was tested. The compounds exhibited good antiproliferative results when compared with the standards cisplatin and 5‐fluorouracil. In silico studies to evaluate pharmacokinetic properties using pkCSM software were also carried out. [ABSTRACT FROM AUTHOR]

In this work, we propose a general methodology to assess the bioactive potential (BP) of extracts in the quest of vegetable-based drugs. To exemplify the method, we studied the anticancer potential (AP) of four endemic species of genus Hypericum (Hypericum canariense L, Hypericum glandulosum Aiton, Hypericum grandifolium Choisy and Hypericum reflexum L.f) from the Canary Islands. Microextracts were obtained from the aerial parts of these species and were tested against six human tumor cell lines, A549 (non-small-cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small-cell lung), T-47D (breast) and WiDr (colon). The methanol–water microextracts were evaluated further for cell migration, autophagy and cell death. The most promising bioactive polar microextracts were analyzed by UHPLC–DAD–MS. The extraction yield, the bioactivity evaluation and the chemical profiling by LC–MS suggested that H. grandifolium was the species with the highest AP. Label-free live-cell imaging studies on HeLa cells exposed to the methanol–water microextract of H. grandifolium enabled observing cell death and several apoptotic hallmarks. Overall, this study allows us to select Hypericum grandifolium Choisy as a source of new chemical entities with a potential interest for cancer treatment. [ABSTRACT FROM AUTHOR]

Natural products represent an excellent source of unprecedented anticancer compounds. However, the identification of the mechanism of action remains a major challenge. Several techniques and methodologies have been considered, but with limited success. In this work, we explored the combination of live cell imaging and machine learning techniques as a promising tool to depict in a fast and affordable test the mode of action of natural compounds with antiproliferative activity. To develop the model, we selected the non-small cell lung cancer cell line SW1573, which was exposed to the known antimitotic drugs paclitaxel, colchicine and vinblastine. The novelty of our methodology focuses on two main features with the highest relevance, (a) meaningful phenotypic metrics, and (b) fast Fourier transform (FFT) of the time series of the phenotypic parameters into their corresponding amplitudes and phases. The resulting algorithm was able to cluster the microtubule disruptors, and meanwhile showed a negative correlation between paclitaxel and the other treatments. The FFT approach was able to group the samples as efficiently as checking by eye. This methodology could easily scale to group a large amount of data without visual supervision. [ABSTRACT FROM AUTHOR]

In the present work, derivatives of phenanthridine-6(5 H )-ones and benzo[ c ]chromenes were efficiently prepared through an intramolecular C-H bond functionalization reaction catalyzed by photochemically synthesized Pd-PVP nanoparticles. The heterocycles were obtained via intramolecular arylation of the corresponding N -methyl- N -aryl-2-halobenzamide or aryl-(2-halo)benzyl ethers using K 2 CO 3 as base in a mixture of H 2 O : DMA as solvent without additives or ligands. High yields of the heterocyclic compounds were achieved (up to 95%) using a moderately low catalyst loading (1-5 mol%) under an air atmosphere at 100 °C. The reaction exhibited very good tolerance to diverse functional groups (OMe, Me, t Bu, Ph, OCF 3 , CF 3 , F, Cl, -CN, Naph), and both bromine and iodine substrates showed great reactivity. Finally, the in vitro antiproliferative activity of phenanthridine-6(5 H )-ones and benzo[ c ]chromenes was evaluated against six human solid tumor cell lines. The more active compounds exhibit activity in the low micromolar range. 1-Isopropyl-4-methyl-6 H -benzo[ c ]chromene was identified as the best compound with promising values of activity (GI 50 range 3.9-8.6 μM). Thus, the benzochromene core was highlighted as a novel organic building block to prepare potential antitumor agents., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Considering early-stage drug discovery programs, the Ugi four-component reaction is a valuable, flexible, and pivotal tool, facilitating the creation of two new amide bonds in a one-pot fashion to effectively yield the desired α-aminoacylamides. Here, we highlight the reputation of this reaction approach to access number and scaffold diversity of a library of isatin-based α-acetamide carboxamide oxindole hybrids, promising anticancer agents, in a mild and fast sustainable reaction process. The library was tested against six human solid tumor cell lines, among them, non-small cell lung carcinoma, cervical adenocarcinoma, breast cancer and colon adenocarcinoma. The most potent compounds 8d , 8h and 8k showed GI 50 values in the range of 1-10 μM., (Copyright © 2024, Marques et al.)

We have applied the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to prepare a library of ten coumarin-azasugar-benzyl conjugates and two phthalimide-azasugar-benzyl conjugates with potential anti-Alzheimer and anti-cancer properties. The compounds were evaluated as cholinesterase inhibitors, demonstrating a general preference, of up to 676-fold, for the inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE). Nine of the compounds behaved as stronger BuChE inhibitors than galantamine, one of the few drugs in clinical use against Alzheimer's disease. The most potent BuChE inhibitor (IC 50 = 74 nM) was found to exhibit dual activities, as it also showed high activity (GI 50 = 5.6 ± 1.1 μM) for inhibiting the growth of WiDr (colon cancer cells). In vitro studies on this dual-activity compound on Cerebellar Granule Neurons (CGNs) demonstrated that it displays no neurotoxicity.

Polyporoid fungi represent a vast source of bioactive compounds with potential pharmacological applications. The importance of polyporoid fungi in traditional Chinese medicine has led to an extensive use of some species of Ganoderma for promoting health and longevity because their consumption is associated with several bioactivities. Nevertheless, bioactivity of some other members of the Polyporaceae family has also been reported. This work reports the antiproliferative and antibacterial activity of crude extracts obtained from fruiting bodies of polypore fungi collected from the central region of Veracruz, Mexico, aimed at understanding the diversity of polypore species with potential pharmacological applications. 29 collections were identified macro- and microscopically in 19 species of polyporoid fungi, belonging to 13 genera. The antiproliferative activity screening of extracts against solid tumor cell lines (A549, SW1573, HeLa, HBL-100, T-47D, WiDr) allow us to identify four extracts with strong bioactivity [half-maximal growth inhibition (GI50) ≤ 50 μg/mL]. After this, a phylogenetic analysis of DNA sequences from the ITS region obtained from bioactive specimens allowed us to identify three extracts as Pycnoporus sanguineus (GI50 = ≤ 10 μg/mL) and the fourth bioactive extract as Ganoderma oerstedii (GI50 = < 50 μg/mL. Likewise, extracts from P. sanguineus showed mild or moderate antibacterial activity against Escherichia coli, Staphylococcus aureus and Xanthomonas albilineas. Bioprospecting studies of polyporoid fungi add to the knowledge of the diversity of macrofungi in Mexico and allow us to select one of the bioactive P. sanguineus to continue the pursuit of bioactive compounds through mycochemical studies.

Complexes [{RuCp(PPh 3 ) 2 -μ-dmoPTA-1κ P :2κ 2 - N , N '-CuCl} 2 -μ-Cl-μ-OCH 3 ](CF 3 SO 3 ) 2 ·(CH 3 OH) 4 (1) and [{RuCp(PPh 3 ) 2 -μ-dmoPTA-1κ P :2κ 2 - N , N '-NiCl} 2 -μ-Cl-μ-OH](CF 3 SO 3 ) 2 (2) have been synthesized and characterized. Their antiproliferative activities were assessed against six human solid tumours showing nanomolar GI 50 values. The effects of 1 and 2 on SW1573 cells colony formation, HeLa cells action mechanism and their interaction with the pBR322 DNA plasmid were evaluated.

In this study, we demonstrate a simple, highly efficient, rapid and convenient series of 2,4-dimethoxy-tetrahydropyrimido[4,5- b ]quinolin-6(7 H )-ones 4a-v. Microwave irradiation facilitates the one-pot multicomponent reaction of different aromatic aldehydes, 6-amino-2,4-dimethoxypyrimidine and dimedone using glacial acetic acid. Metal-free multicomponent synthesis, shorter reaction time, higher product yield, easy product purification without column chromatography and outstanding green credential parameters are the key features of this protocol. We analysed 4a-v against six human tumour cell lines for antiproliferative activity. 4h, 4o, 4q and 4v show good antiproliferative activity with a good in silico ADMET profile. Furthermore, 4h, 4o, 4q and 4v also show drug-likeness properties by obeying drug-like filters., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)