Design, synthesis and antiproliferative activity evaluation of new 3,7-disubstituted pyrrolo[2,3-c]pyridines

A series of N-13-arylated evodiamine derivatives (3a–3v) were designed and synthesized via a Cu-catalyzed late-stage diversification of the bioactive natural product evodiamine. The antitumor activities of these synthesized derivatives against HCT-116, 4T1, and SU-DHL-6 cells were evaluated in vitro, demonstrating that direct introduction of aryl groups at the N-13 position through C–N coupling led to unsatisfactory cytotoxicity. Based on previous studies, the preliminary structure–activity relationship analysis indicated that inserting a suitable pharmacophore fragment between the N-13 position and the introduced aryl group can enhance the anti-tumor activity of N-13 evodiamine derivatives containing aromatic functional groups. This study provides helpful insights for the further development of antitumor evodiamine analogues.

Evaluation of physicochemical properties, antioxidant capacity, and antiproliferative activity against human cancer cell lines of ethanolic extract of irradiated Sonchus arvensis

Adamantane-tetrazole hybrid derivatives: synthesis, crystal structure, molecular docking, molecular dynamics simulations and in vitro evaluation of antibacterial, antifungal, and anti-proliferative activities

ABSTRACT Mixed ligand new cobalt, nickel and copper complexes were synthesized from caffeine and pyrrolidinium ionic liquid embedded Schiff base, 1‐{2‐(5‐bromo‐2‐hydroxybenzylideneamino) ethyl}‐1‐methyl‐pyrrolidinium [BF 4 ] as the primary ligand. All the metal complexes were obtained as powders having significant bright color and analyzed by different spectroscopic methods like CHN analysis, PXRD, SEM, EDS, 13 C‐NMR, 1 H‐NMR, FT‐IR, ESI‐MS, UV‐visible and magnetic moments measurements. The obtained spectral data indicated octahedral coordination of the ligand surrounding the metal center. The synthesized metal chelates as well as the ionic liquid embedded Schiff base were examined against Bacillus cereus KTWOL4 and Escherichia coli K12 strains and very significant results were observed for the Schiff base and the nickel complex. Evaluation of antiproliferative activity of the compounds against lung cancer (A‐549) and human normal liver (WRL‐68) cell lines showed that the metal complexes had higher anticancer activity against the human lung carcinoma compared to the Schiff base, while they had significantly lower effects on normal cells.

Background/Objectives: Cancer is among the leading causes of mortality worldwide. In 2022 alone, the global cancer death toll stood at 9.74 million. Projections indicate that this figure will rise to 10.4 million by 2025. Methods: A new series of benzimidazolone-bridged hybrid compounds containing thiophene, furan, oxadiazole, piperazine, and coumarin moieties was synthesized and structurally characterized by 1H-NMR, 13C-NMR (APT), and elemental analysis. Their cytotoxic effects were evaluated by MTT assay against human lung (A549), human breast (MCF-7), and human cervical (HeLa) cancer cell lines, and the non-cancerous HEK293 cell line after 48 h exposure over a concentration range of 0.5–250 µM. IC50 values were determined, and Selectivity Indexes (SI) were calculated using HEK293 as the reference normal cell line. Molecular docking studies were carried out using the Glide XP protocol against VEGFR2 (PDB ID: 4ASD) and CDK4–Cyclin D3 (PDB ID: 7SJ3), with sorafenib and abemaciclib as reference inhibitors. Results: The results of anticancer activity were compared with doxorubicin (IC50 ± SD (µM)/SI: 4.3 ± 0.2/1.20 for A549, 6.4 ± 0.37/0.77 for MCF-7, 3.4 ± 0.19/1.54 for HeLa), a drug used for cancer chemotherapy. The structures of the newly synthesized hybrid compounds were identified by 1H-NMR, 13C-NMR (APT), and elemental analysis data. These hybrid compounds represent a promising class of anticancer agents. Several compounds demonstrated marked and concentration-dependent cytotoxicity across all cancer cell lines, with HeLa cells showing the highest overall sensitivity. The introduction of an oxadiazole ring (compound 7) and coumarin substituents (compounds 12b–12d) markedly improved anticancer activity and selectivity, yielding low-micromolar IC50 values in HeLa cells (10.6–13.6 µM) and high Selectivity Indexes (SI = 2.0–3.63). Compound 6 also exhibited balanced potency across A549, MCF-7, and HeLa cells (IC50 = 28.3–31.2 µM) with SI values ≥ 2.0. Compound 9 showed strong cytotoxicity across all cancer cell lines; its moderate SI values indicate lower discrimination between malignant and non-malignant cells. Taken together, these findings identified compounds 7, 12b–12d, 6, and 12c as the most promising benzimidazolone-based candidates, displaying both potent cytotoxicity and favorable selectivity over non-malignant HEK293 cells. Conclusions: Among the synthesized molecules, the oxadiazole derivative (7) and the coumarin-based hybrids (12b–12d) exhibited the strongest combination of cytotoxic activity and selectivity, reflected by their low IC50 values and high SI ratios. Notably, compound 12c combined strong biological activity with the highest predicted VEGFR2 affinity in the series, highlighting it as a particularly promising scaffold. While compound 9 exhibited excellent docking scores toward both VEGFR2 and CDK4, its lower selectivity suggests a need for further structural refinement. Overall, the biological and computational findings converge to identify these benzimidazolone hybrids as credible lead candidates for future anticancer optimization.

Ruthenium(II) complexes of 1-(2-picolyl)-1,2,3-triazole-appended 2-arylbenzothiazoles: synthesis, characterization, in vitro and in silico evaluation of anti-proliferative activity

A series of N-hydroxy-2-[4-(2-R1,3-R2,6-R3-quinolin-4-yl)phenyl]acetamides 4a–4n (R1–R3 = Me, Et, Cl, Ph) was synthesized, screened for HDAC8 inhibition and antiproliferative activity, and analyzed via in silico molecular docking. The synthesis of the hydroxamic acid-functionalized quinoline scaffolds involved the Friedlander reaction followed by Friedel–Craft alkylation and ester hydrolysis. The in vitro HDAC8 inhibition potential and antiproliferative activity of the synthesized compounds were assessed by the MTT assays. Molecular docking was performed of the products to the HDAC8 target protein (PDB ID: 5FCW) was performed to determine the binding energies and sites, as well as nature of interactions In the in vitro HDAC8 inhibition activity, 4g showed a slightly higher (IC50 = 9.53 µM), while 4a exhibited a slightly lower activity (IC50 = 21.24 µM) than the other compounds. Scaffold 4g exhibited good in vitro anticancer activity (IC50 = 3.69 µM) against the COLO 205 cell line, and scaffold 4h was found to be active against two cancer cell lines: HCT 116 (IC50 = 6.91 µM) and COLO320 DM (IC50 = 8.91 µM). Molecular docking predicted high binding affinities of compounds 4g and 4n (–8.1 and –7.9 kcal/mol) to the HDAC8 target protein. The results highlight the HDAC8 inhibitory and anticancer potential of the new hydroxamic acid–appended quinoline derivatives, identifying compound 4g as a particularly promising candidate for further development.

A series of novel γ-halo-δ-lactones and δ-halo-γ-lactones bearing a phenolic ring at the β-position were synthesized from vanillin. The divergent seven-step synthetic route commenced with the benzyl protection of the hydroxy group of the starting material, followed by a four-step transformation that led to the corresponding β-aryl-γ,δ-unsaturated carboxylic acids. Subsequent halolactonization (iodo-, bromo-, and chlorolactonization), followed by selective benzyl deprotection, gave the target halolactones. The structures of all intermediates and final lactones were confirmed by comprehensive spectroscopic analyses, including NMR and HRMS. The resulting halolactones were evaluated for antiproliferative activity against two canine (CLBL-1, CLB70) and two human (T-24, CaCo-2) cancer cell lines, as well as non-cancerous mouse embryonic fibroblasts (NIH/3T3). Hemolytic assays were performed to assess toxicity against human red blood cells (RBCs). Among the tested lactones, the transδ-iodo-γ-lactone was the most active, particularly against CLBL-1 and T-24 cells. All compounds demonstrated no inhibitory effects on normal fibroblasts and no hemolytic toxicity. This favorable selectivity profile positions this group of lactones, particularly trans-δ-iodo-γ-lactone, as a promising candidate for further development as potential anticancer agents.

ABSTRACT A new “one‐pot” metal‐free stereoselective method for the synthesis of diversely functionalized pyrrolidine‐2‐ones from N‐alkyl‐ or N‐arylsulfonamidoacetophenones was developed. The method was used for the synthesis of a new biologically active scaffold with three stereocenters based on diversely functionalized pyrrolidine‐2‐one. The absolute configuration of stereocenters in the new scaffold was established. The novel compounds were obtained with modest to moderate yields. The antiproliferative activities of the new compounds were tested on several cancer cell lines. The majority of the synthesized compounds showed low micromolar antiproliferative activities.

This study aimed to evaluate the biological activities of the ethanol extract obtained from the aerial parts of Dryopteris raddeana (Fomin) Fomin. Total antioxidant capacity (TAS), total oxidant level (TOS) and oxidative stress index (OSI) values ​​determined by Rel Assay kits using ethanol extract obtained from aerial parts of the plant were determined as 5.099±0.076 mmol/L, 7.354±0.107 µmol/L and 0.144±0.004, respectively. These results show that D. raddeana exhibits a balanced oxidative profile and has low oxidant load. In anticholinesterase activity analyses, the inhibitory effect of the extract against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes was determined as 58.99±1.48 µg/mL and 83.51±1.59 µg/mL, respectively. In the evaluation of antiproliferative effect, it was observed that extract concentrations in the range of 25–200 µg/mL applied to A549 human lung cancer cell line decreased cell viability in a dose-dependent manner. A significant decrease in cell viability was detected especially at concentrations of 100 and 200 µg/mL. In conclusion, in this study, it was determined that the plant could be an antioxidant, antimicrobial and antiproliferative source for these biological activities of D. raddeana.

The purpose of this study was to ascertain the phytochemical composition and antiproliferative properties of methanolic extract made from the roots, branches, leaves, and flowers of Echinophora chrysantha (EC). Phytochemical content was determined using RP-HPLC. Sixteen metabolites were identified as a result of RP-HPLC examination of EC extracts. Using the XTT technique, antiproliferative activity tests were examined on HT29 and A549 cell lines. All extracts strongly inhibited the examined cell lines. In particular, the branch extract shown outstanding antiproliferative activity against A549 (IC50:7.40 μg/mL) and HT-29 (IC50:1.70 μg/mL). Echinophora chrysantha's traditional use and therapeutic usefulness are further reinforced by the identification of its metabolites and assessment of its bioactivity.

Design, synthesis, and antiproliferative activity evaluation of novel cyclic secondary amine containing dithiocarbamate derivatives as potent EGFR inhibitors

Retraction notice to “Solvent-solute polarity, electrophilic, steric effects, reactive sites, themodynamic quantities discussion and biological evaluation of lung cancer antiproliferative activities of spirobrassinin derivatives” [J. Mol. Liq. 385 (2023) 122382

Eulophia nuda Lndl., a terrestrial medicinal orchid, is well known for its ethnomedicinal applications in treating bronchitis, tuberculosis, tumours, snake bites and arthritis. This study aimed to identify the phytoconstituents of E. nuda extract (ENE) and evaluate its antioxidant, antityrosinase, anticancer and antimicrobial activities. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry analysis identified 33 compounds, 31 of which were reported for the first time, with phenols, terpenoids and carboxylic acids as dominant classes. ENE exhibited strong antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals with half-maximal inhibitory concentration (IC50) values of 40.42 ± 0.31 and 12.94 ± 0.22 µg/mL, respectively. Antimicrobial studies against six bacterial strains showed zones of inhibition ranging from 11 to 15 mm, with strong inhibitory activity against E. faecalis (minimum inhibitory concentration: 31.25 µg/mL). The extract demonstrated moderate antityrosinase activity (IC50: 357.36 µg/mL) compared to Kojic acid. Additionally, ENE showed significant antiproliferative effects against Panc-1, HepG2, and PC3 cancer cell lines, with IC50 values of 29.39, 38.13 and 46.97 µg/mL, respectively. These findings highlight the therapeutic potential of ENE, supported by its diverse phytoconstituents and bioactivities, paving the way for its development in both traditional and modern medicine.

This study describes the synthesis of O-alkylated benzaldehydes 1-8, Schiff bases 9-28, and benzoxazole derivatives 29-48 using microwave, ultrasound, and mechanochemical reactions, as well as reactions in deep eutectic solvents in excellent yields, and their antiproliferative and antibacterial activities. The in vitro evaluation of antiproliferative activity for the newly synthesised benzoxazole derivatives 29-48 against a diverse panel of human cancer cell lines, such as LN-229, Capan-1, HCT-116, NCI-H460, DND-41, HL-60, K-562, and Z-138 demonstrated that the majority of these benzoxazole derivatives displayed promising anticancer activity, particularly against non-small cell lung cancer (NSCLC) cells (NCI-H460). Notably, several derivatives showed enhanced activity compared to the included reference drug, etoposide. Considering the influence of substituents at position 5 of the benzoxazole ring and positions 3 and 4 of the phenyl ring on the antiproliferative activity, it is evident that derivatives 41-48 bearing a methoxy group at position 3 generally exhibit higher activity compared to compounds 29-40, which lack substitution at position 3. Furthermore, derivatives substituted at position 4 with a morpholine substituent, as well as those with an N,N-diethyl group, exhibited higher activity compared to other evaluated benzoxazole derivatives. The in vitro antibacterial evaluation against Gram-positive and Gram-negative bacteria revealed that benzoxazole derivative 47 exhibited notable activity, against the Gram-negative bacterium Pseudomonas aeruginosa (MIC = 0.25 μg/mL) and the Gram-positive bacterium Enterococcus faecalis (MIC = 0.5 μg/mL). The results point out that this class of benzoxazoles can be efficiently synthesized using eco-friendly methods and represent promising candidates for further design and optimization aimed at developing potent antiproliferative agents.

ObjectiveCurcumin is a polyphenol extracted from the roots of Curcuma longa L. It is a multifunctional biological substance that has notable antioxidant, anti-inflammatory, anti-cancer, and antibacterial properties, as reported in numerous previous papers. However, curcumin has limited bioavailability due to its low water solubility. Furthermore, pH, temperature, and light all have the potential to decrease curcumin's biopharmaceutical activities. Silver nanoparticles have excellent antibacterial characteristics and are used in various applications. The main objective of this work was to synthesize the gelatin microgel-stabilized silver nanoparticles loaded with curcumin (GelCurAg complex) to increase the biopharmaceutical activities of the complex.MethodsNumerous techniques, including UV-vis spectroscopy, FTIR spectroscopy, Zetasizer Nano instruments, TEM images, and XDR patterns, were used for investigating the characterization of the GelCurAg complex. The various methods, such as the DPPH antioxidant assay, cytotoxicity analysis, and the agar-well diffusion method, were used for the analysis of the biopharmaceutical activities of the GelCurAg complex.ResultsWe successfully synthesized and characterized the GelCurAg complex, consisting of gelatin, curcumin, and silver nanoparticle biofilms using polyvinylpyrrolidone. The average nanoparticle size was 50 nm. The GelCurAg complex improved water solubility and dispersion compared with the single curcumin component. The IC50 value for antioxidant activity was 4.87 μg/mL, and for antiproliferation on SK-MEL-28, it was 3.98 µg/mL. GelCurAg solution provided remarkable antibacterial activities against four bacterial strains: Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The GelCurAg complex showed better antibacterial activities than the single curcumin component, with the antibacterial inhibition zone in the range of 0.9­–1.6 cm.ConclusionsThe GelCurAg complex enhanced the solubility and dispersion of curcumin in water while increasing its antibacterial activity compared to curcumin. The GelCurAg complex has excellent biopharmaceutical properties to suggest its various applications in the future.

Abstract Earlier, we have reported penicillic acid to be the major secondary metabolite from ethyl acetate extract of the broth produced by a fungal strain named as Penicillium polonicum . It exhibited high inhibitory activity against a plant pathogen Pythium aphanidermatum . In order to establish structure‐activity relationship of penicillic acid, a series of chemical transformations of this constituent has been carried out under different reaction conditions, alteration of solvents and changing reagents. The yield was processed by various standard separation technique followed by preparative TLC and crystallization where it possible. The structural characterization of purified derivatives has been determined by chemical, spectral and spectrometric methods. The evaluation of antiproliferative activity of them was conducted on different human cancer cell lines. It has also been evaluated for antibiosis against P. aphanidermatum . The penicillic acid and dihydro‐penicillic acid exhibited moderate activity against pancreatic (HPAC‐1376), colon (HT‐29) and thyroid (MDA‐T32) cancer cell lines with IC 50 values 15.66/16.09, 18.74/18.37, and 19.18/19.17 µg/mL respectively. Unlike the parent compound and none of the derivatives viz . dihydropenicillic acid ( 2 ), bromohydroxy penicillic acid ( 3 ), dibromo‐penicillic acid ( 4 ), bromosuccinmidyl‐penicillic acid ( 5 ), bromohydro‐penicillic acid ( 6 ), demethoxy‐penicillic acid ( 7 ), sulphated‐penicillic acid ( 8 ), hydroxyl penicillic acid ( 9 ), and bromo‐amino penicillic acid ( 10 ) showed inhibitory activity against P. aphanidermatum .

Discovery of naphthoquinone-furo-piperidone derivatives as dual targeting agents of STAT3 and NQO1 for the treatment of breast cancer.

In vitro evaluation of antioxidant, probiotic, and antiproliferative activity of Ganoderma lucidum-extracted polysaccharides for the prevention of complication associated with gastrointestinal inflammatory diseases