Osteosarcoma is the most common primary bone malignancy with a challenging prognosis marked by a high rate of metastasis. The limited success of current treatments may be partially attributed to an incomplete understanding of osteosarcoma pathophysiology and to the absence of reliable in vitro models to select the best molecules for in vivo studies. Among the natural compounds relevant for osteosarcoma treatment, Licochalcone A (Lic-A) and chalcone derivatives are particularly interesting. Here, Lic-A and selected derivatives have been evaluated for their anticancer effect on multicellular tumor spheroids from MG63 and 143B osteosarcoma cell lines. A metabolic activity assay revealed Lic-A, 1i, and 1k derivatives as the most promising candidates. To delve into their mechanism of action, caspase activity assay was conducted in 2D and 3D in vitro models. Notably, apoptosis and autophagic induction was generally observed for Lic-A and 1k. The invasion assay demonstrated that Lic-A and 1k possess the ability to mitigate the spread of osteosarcoma cells within a matrix. The effectiveness of chalcone as a natural scaffold for generating potential antiproliferative agents against osteosarcoma has been demonstrated. In particular, chalcones exert their antiproliferative activity by inducing apoptosis and autophagy, and in addition they are capable of reducing cell invasion. These findings suggest Lic-A and 1k as promising antitumor agents against osteosarcoma cells.

We have synthesized a series of novel coumarin-steroid and triterpenoid hybrids and evaluated their potential anticancer activity through molecular docking calculations and in vitro antiproliferative assays. These hybrids, derived from estrone and oleanolic acid, were linked via hydrocarbon spacers of varying lengths. Molecular docking studies against human aromatase revealed strong interactions, particularly for compound 11d, which exhibited significant binding affinity (-12.6308 kcal/mol). In vitro assays demonstrated that compounds 6b and 11d had notable antiproliferative effects, with GI50 values of 5.4 and 7.0 μM against WiDr (colon) and HeLa (cervix) cancer cells, respectively. These findings highlight the potential of these hybrids as novel anticancer agents targeting aromatase, warranting further investigation and optimization.

In this paper, we present the synthesis and characterization of two known sulfonyl hydrazides (1 and 2) and their new sulfonyl hydrazone derivatives (9-20), as well as in vitro and in silico investigations of their cytotoxic properties against human lung (A549) and human breast (MCF-7) cancer cell lines. The target compounds (9-20) obtained in high yields were synthesized for the first time by a multi-step reaction, and their structures were confirmed by elemental analysis and various spectral techniques, including FT-IR, 1H-, and 13C-NMR. The antiproliferative profiles of these compounds (1, 2, and 9-20) in this study were determined at concentrations of 200, 100, 50, and 25 µM against selected cancer cell lines for 72 h using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. Except for compounds 1 and 2, other compounds (9-20) demonstrated cytotoxic activity at concentrations lower than 200 µM. The newly synthesized compounds (9-20) demonstrated antiproliferative activities at a micromolar level, with IC50 values in the range of 29.59-176.70 μM for the A549 cell line and 27.70-170.30 μM for the MCF-7 cell line. Among these compounds, compound 15 (IC50 = 29.59 μM against A549 cell line and IC50 = 27.70 μM against MCF-7 cell line) showed the highest cytotoxic activity against these two cancer cell lines compared to the reference drug cisplatin (IC50 = 22.42 μM against A549 cell line and IC50 = 18.01 μM against MCF-7 cell line). From docking simulations, to establish a plausible binding mode of compounds, we noticed that compound 15 demonstrated the highest affinity (-6.8508 kcal/mol) for estrogen receptor-beta (ERbeta) compared to others, suggesting promising ERbeta binding potential. Most compounds followed Lipinski\'s rule of five, with acceptable logP values. Additionally, all had mixed gastrointestinal absorption and limited blood-brain barrier permeability. Overall, our study proposed new sulfonyl hydrazones as a potential class of anticancer agents.

In this work, a series of new diarylpyrimidine derivatives as microtubule destabilizers were designed, synthesized, and evaluated for anticancer activities. Based on restriction configuration strategy, we introduced the pyrimidine moiety containing the hydrogen-bond acceptors as cis-olefin bond of CA-4 analogs to improve structural stability. Compounds 11a-t exerted antiproliferative activities against three human cancer cell lines (SGC-7901, HeLa, and MCF-7), due to tubulin polymerization inhibition, showing high selectivity toward cancer cells in comparison with non-tumoral HSF cells, as evidenced by MTT assays. In mechanistic investigations, compound 11s remarkably inhibited tubulin polymerization and disorganized microtubule in SGC-7901 cells by binding to tubulin. Moreover, 11s caused G2/M phase cell cycle arrest in SGC-7901 cells in a concentration-dependent manner. Furthermore, molecular modeling analysis revealed that 11s interacts with tubulin through binding to the colchicine site. In addition, the prediction of physicochemical properties disclosed that 11s conformed well to the Lipinski\'s rule of five. This work offered a fresh viewpoint for the discovery of new tubulin-targeting anticancer drugs.

Allium roseum is amongst the most important wild medicinal plants. It is known for its diverse biological properties, including antioxidant, antibacterial and antidiabetic activities. In this work, the polysaccharides (PARLs) were ultrasonically extracted from Allium roesum leaves then purified and analyzed by several techniques. Chemical composition and GC-MS analysis showed that the obtained polysaccharides were composed mainly of glucose (40.20 %), mannose (25.30 %), fructose (10.60 %) and galacturonic acid (15.11 %). Moreover, PARLs exhibited a potent antioxidant effect with higher capacities up to 69.61 % and 71.72 % for DPPH and ABTS free radicals, respectively. Furthermore, PARLs significantly modulated inflammatory response by reducing TNF-α, IL-6, and IL-8 pro-inflammatory mediators and promoting the anti-inflammatory IL-10 mediator in LPS stimulated THP-1 derived macrophages. The in-vivo tests proved that the extract was able to decrease carrageenan-induced rat paw swelling by around 68.15 % after 4 h of treatment. PARLs, significantly reduced the growth of U87 (glioblastoma) and IGROV-1 cancer cells with IC50 values of about 4.27 and 7.89 mg/mL respectively. This research clearly shows that Allium roseum polysaccharides can be used as natural antioxidants with anti-inflammatory and anticancer properties.

Steroid dimers of natural and synthetic origin possess an unusual and complex molecular architecture that may lead to the realization of peculiar effects in biological systems, in particular in different cancer cell lines. In the present work, diastereoselective ring-opening of mono- and polyoxiranes, containing a cyclooctane core, by azide-anion was performed to yield a series of azidoalcohols with different types of symmetry. The products were involved in copper-catalyzed azyde-alkyne cycloaddition (CuAAC) reaction with ethinylestradiol and ethinyltestosterone, and the resulting steroids and steroid dimers with triazole linkers were screened for their antiproliferative activity via (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) assay. All the compounds revealed cytotoxicity toward several cancer cell lines. The effect of the most potent compound, containing two estradiol moieties, on the microtubules (MT) dynamics was investigated by immunofluorescent microscopy. The disruption of the majority of interphase cell cytoplasmic MT and mitotic event disturbances in the presence of the studied compound were observed. The latter effect caused the appearance of numerous multinucleated cells.

UNASSIGNED: To study constituents of the leaves of Macaranga hemsleyana, and evaluate their inhibitory effects against NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation, and antiproliferative activity.
UNASSIGNED: The constituents were isolated and purified by column chromatography on MCI gel CHP20P/P120, silica gel, Sephadex LH-20, and HPLC. The structures of compounds were determined by 1D, 2D NMR, and HR-ESI-MS data. The inhibitory effect of compounds on inflammasome activation was determined by lactate dehydrogenase (LDH) procedure. The antiproliferative activity was evaluated using MTT assay.
UNASSIGNED: The study led to the isolation of 23 compounds, including one new compound, identified as (2Z)-3-[4-(β-D-glucopyranosyloxy)-2\'-hydroxy-5\'-methoxyphenyl]-2-propenoic acid (1), together with 22 known compounds recognized as 1,4-dihydro-4-oxo-3-pyridinecarbonitrile (2), methyl 4-methoxynicotinate (3), 4-methoxynicotinonitrile (4), 1-(3-O-β-D-glucopyranosyl-4,5-dihydroxyphenyl)-ethanone (5), neoisoastilbin (6), isoastilbin (7), aromadendrin (8), neoastilbin (9), astilbin (10), quercitrin (11), neoschaftoside (12), apigenin 6,8-bis-C-α-L-arabinoside (13), vitexin (14), bergenin (15), scopoletin (16), glucopyranoside salicyl (17), koaburside (18), benzyl β-D-glucoside (19), icariside B5 (20), roseoside (21), loliolide (22), and adenosine (23). The tested compounds did not show LDH inhibition nor antiproliferative activity.
UNASSIGNED: Compound 1 was a new glycoside. Compounds 2 and 3 were obtained for the first time from natural source. The 22 known compounds constituted of alkaloids (2-4, 23), phenolics (5, 15, 17, 18), flavonoids (6-14), coumarin (16), benzyl glycoside (19), and norsesquiterpenes (20-22). All the compounds, 1-23, were revealed from M. hemsleyana for the first time. This is the initial uncovering of molecules 1-10, 12, 13, 17-19, and 23 from the genus Macaranga. The isolated compounds, 11, 14-16, and 20-22 established taxonomic classification of M. hemsleyana in Euphorbiaceae family. Flavonoids were outstanding as chemosystematic markers of Macaranga genus.

This study focuses on the synthesis and structural characterization of new compounds that integrate thiazolidine-2,4-dione, acridine moiety, and an acetamide linker, aiming to leverage the synergistic effects of these pharmacophores for enhanced therapeutic potential. The newly designed molecules were efficiently synthesized through a multi-step process and subsequently transformed into their hydrochloride salts. Comprehensive spectroscopic techniques, including nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), infrared (IR) spectroscopy, and elemental analysis, were employed to determine the molecular structures of the synthesized compounds. Biological evaluations were conducted to assess the therapeutic potential of the new compounds. The influence of these derivatives on the metabolic activity of various cancer cell lines was assessed, with IC50 values determined via MTT assays. An in-depth analysis of the structure-activity relationship (SAR) revealed intriguing insights into their cytotoxic profiles. Compounds with electron-withdrawing groups generally exhibited lower IC50 values, indicating higher potency. The presence of the methoxy group at the linking phenyl ring modulated both the potency and selectivity of the compounds. The variation in the acridine core at the nitrogen atom of the thiazolidine-2,4-dione core significantly affects the activity against cancer cell lines, with the acridin-9-yl substituent enhancing the compounds\' antiproliferative activity. Furthermore, compounds in their hydrochloride salt forms demonstrated better activity against cancer cell lines compared to their free base forms. Compounds 12c·2HCl (IC50 = 5.4 ± 2.4 μM), 13d (IC50 = 4.9 ± 2.9 μM), and 12f·2HCl (IC50 = 4.98 ± 2.9 μM) demonstrated excellent activity against the HCT116 cancer cell line, and compound 7d·2HCl (IC50 = 4.55 ± 0.35 μM) demonstrated excellent activity against the HeLa cancer cell line. Notably, only a few tested compounds, including 7e·2HCl (IC50 = 11.00 ± 2.2 μM), 7f (IC50 = 11.54 ± 2.06 μM), and 7f·2HCl (IC50 = 9.82 ± 1.92 μM), showed activity against pancreatic PATU cells. This type of cancer has a very high mortality due to asymptomatic early stages, the occurrence of metastases, and frequent resistance to chemotherapy. Four derivatives, namely, 7e·2HCl, 12d·2HCl, 13c·HCl, and 13d, were tested for their interaction properties with BSA using fluorescence spectroscopic studies. The values for the quenching constant (Ksv) ranged from 9.59 × 104 to 10.74 × 104 M-1, indicating a good affinity to the BSA protein.

Alkaloid-based urea derivatives were produced with high yield through the reaction of anabasine and cytisine with isoxazolylphenylcarbamates in boiling benzene. Their antitumor activity, in combination with the commonly used five anticancer drugs, namely cyclophosphane, fluorouracil, etoposide, cisplatin, ribomustine with different mechanisms of action, was investigated. Based on the quantum chemical calculations data and molecular docking, hypotheses have been put forward to explain their mutual influence when affecting C6 rat glioma model cells.

The total synthesis of two new marine natural products, (±)-marinoaziridine B 7 and (±)-N-methyl marinoaziridine A 8, was accomplished. The (±)-marinoaziridine 7 was prepared in a six-step linear sequence with a 2% overall yield. The key steps in our strategy were the preparation of the chiral epoxide (±)-5 using the Johnson Corey Chaykovsky reaction, followed by the ring-opening reaction and the Staudinger reaction. The N,N-dimethylation of compound (±)-7 gives (±)-N-methyl marinoaziridine A 8. The NMR spectra of synthetized (±)-marinoaziridine B 7 and isolated natural product did not match. The compounds are biologically characterized using relevant in silico, in vitro and in vivo methods. In silico ADMET and bioactivity profiling predicted toxic and neuromodulatory effects. In vitro screening by MTT assay on three cell lines (MCF-7, H-460, HEK293T) showed that both compounds exhibited moderate to strong antiproliferative and cytotoxic effects. Antimicrobial tests on bacterial cultures of Escherichia coli and Staphylococcus aureus demonstrated the dose-dependent inhibition of the growth of both bacteria. In vivo toxicological tests were performed on zebrafish Danio rerio and showed a significant reduction of zebrafish mortality due to N-methylation in (±)-8.