The search for novel potent anticancer agents is considered a rapidly advancing field and viewed as a constantly evolving area within medicinal chemistry. Twelve new compounds with quinoline side chains connected to bis-oxadiazoles and terminal lipophilic aryl portions with substantial substituent functions were created and synthesized using the EDC coupling reaction in an effort to find new treatments for the cancer epidemic. These compounds were structurally deduced using modern spectroscopic techniques (1H-,13C–NMR, and HRMS). Based on the EGFRWT inhibitory effects, compounds 7c and 7 l exhibited the most potent inhibitory activity with IC50 values of1.75 ± 1.10 μM and 1.60 ± 0.25 μM, when compared to Erlotinib (IC50 = 2.04 ± 0.78 μM). Additionally, it demonstrated notable activity against HT-29 cells, with an IC50 value of 6.65 ± 0.47 μM. In contrast, compound 7 l showed the highest selectivity for MCF-7 inhibition (IC50 = 5.67 ± 2.70 μM), outperforming the reference drug doxorubicin, which displayed an IC50 value of 6.44 ± 1.39 μM. Compound 7f inhibited cell viability by 97.42%, indicating it is the least cytotoxic compared to 7a and 7 l on the normal NCM460 cell line. The binding interactions of the best inhibitory ligands within the active region of breast cancer in EGFR were further verified by molecular docking predictions, which highlighted the significant hydrophobic and hydrogen-bonding interactions (PDB code: 1M17). The drug-like characteristics of these chemical structures (7a–7l) were confirmed by pharmacokinetic investigation of the newly synthesized oxadiazoles, which revealed positive qualities with regard to absorption, distribution, metabolism, excretion, and toxicity (ADME–T). As a result, it is strongly advised that these agents be studied further in clinical trials.

Trefoil Factor 3 (TFF3) is an oncogenic protein implicated in breast cancer progression through regulation of PI3K-AKT, MAPK, STAT3, and NF-κB signaling pathways. Targeting TFF3 therefore represents a promising therapeutic strategy. In this study, chromene-3-carbonitrile derivatives were synthesized using nano-TiO2 as an efficient catalyst and evaluated for their anticancer potential against TFF3 in MCF-7 breast cancer cells through combined in vitro and in silico approaches. Thermodynamic feasibility of the synthetic process was assessed using free energy calculations. Cytotoxicity of the synthesized compounds was determined in MCF-7 cells, while molecular docking studies were performed to investigate binding interactions with TFF3. Protein expression analysis was performed using western blotting to confirm TFF3 inhibition. Several derivatives demonstrated significant cytotoxic activity, with lead compounds F8, F10, F12, and F13 exhibiting IC50 values of 0.751, 1.70, 0.68, and 0.52 µM, respectively. Docking studies revealed strong binding affinity and favorable interactions with TFF3 and energy profiling supported the thermodynamic viability of synthetic route. Western blot results further confirmed downregulation of TFF3 expression. Overall, these findings identify chromene-3-carbonitrile derivatives as potent TFF3-targeting agents with potential therapeutic relevance for breast cancer.

This study reports the synthesis of triazole-rhodanine hybrid compounds (4a-c) via copper-catalyzed click chemistry as multi-target anticancer agents for non-small-cell lung cancer (NSCLC), achieving yields of 78–92%. Comprehensive structural characterization was accomplished through spectroscopic analysis (FT-IR,1H NMR,1³C NMR, elemental analysis, and HRMS). The synthesized derivatives demonstrated significant anticancer activity with IC50 values ranging from 47.71–70.10 μM against A549 cells and selectivity indices (SI) of 1.28–3.56. Molecular docking simulations revealed strong binding affinities (ΔG = −8.41 to −10.42 kcal/mol) against critical oncogenic targets: nuclear factor kappa B (NF-κB), Cyclin D1, phosphorylated AMP-activated protein kinase (p-AMPK), and vascular endothelial growth factor 1 (VEGF1), establishing a multi-target therapeutic mechanism. Chitosan-based nanoformulations substantially enhanced therapeutic efficacy by 2.5–4.2-fold, with nanoparticles (size: 59.2–85.2 nm, PDI: 0.807–1.00) achieving IC50 values of 37.58–46.02 μM. The N-4b nanoformulation exhibited the highest therapeutic potential (IC50 = 37.58 μM) with excellent drug-likeness properties and superior selectivity (SI = 4.32). This integrated synthetic and computational approach provides a novel framework for developing multi-target triazole-rhodanine hybrids as promising NSCLC therapeutics.

In this investigation, we successfully synthesized fused pyridonaphthyridines, a newly identified class of fused heterocyclic compounds, through an efficient multicomponent reaction. The methodology involved utilizing 3-(2-hydroxyphenyl)-3-iminopropanamide, 2-(1,3-diimino-1,3-dihydro-2H-inden-2-ylidene) malononitrile, alkyl bromides, and activated acetylenic derivatives within an aqueous medium at ambient temperature. Notably, the process was facilitated by a reusable catalyst composed of Ag/Fe3O4@GO. The newly synthesized compounds were subsequently evaluated for their antiproliferative potential against MCF-7 breast cancer and HCT-15 colon cancer cell lines using the Sulfo-rhodamine B (SRB) assay, along with their antioxidant capabilities. Among the compounds tested, derivatives 5c and 5 g demonstrated notably superior antiproliferative activity relative to their counterparts. To further explore their interaction with biological macromolecules, these two compounds underwent UV-Vis spectral analysis to determine their binding affinities to DNA and bovine serum albumin (BSA). The results revealed affinity constants of K5c-DNA = 7.32 × 10³ M−1, K5g-DNA = 2.09 × 104 M−1, K5c-BSA = 5.32 × 104 M−1, and K5g-BSA = 8.24 × 104 M−1, respectively. The outcomes of this study could provide novel insights into the relationship between the chemical structure of these pyridonaphthyridine analogs and their capacity to inhibit cancer cell proliferation.

Over the past few decades, discovering new anticancer drugs was considered one of the biggest challenges for researchers. In this study, two series of acylhydrazones Z1-6 and hydrazones K1-6 were synthesized via reacting isoniazid or 2-hydrazinopyridine with some aromatic heterocyclic aldehydes under acidic conditions. The structures of all compounds were proven spectrophotometrically using proton nuclear magnetic resonance (1HNMR) and carbon-13 NMR (13CNMR), in addition to liquid chromatography-mass (LCMS) spectra, infrared (IR) spectra, and elemental analyses. Our compounds were evaluated for their anticancer activity against three types of cancer cells: colon HCT-116, lung A-549, and MCF-7 breast Adenocarcinoma cancer cells by the SRB method. Compounds Z3 and K4 showed the highest inhibition against colon cancer cells with IC50 values of 1.59 and <1 μM, respectively. Moreover, flowcytometric analysis revealed the ability of Z3 to cause cell cycle arrest at sub G1 phase and S phase in HCT-116 colon cancer cell line, in addition to prominent apoptotic effects. Subsequently, molecular docking was conducted to gain insight into the plausible mechanism of action for the most active compounds Z3 and K4 and it suggested Topoisomeras I as a potential biological target of the new counterparts. Absorption, Distribution, Metabolism Excretion, and Toxicity (ADMET) study predicted physicochemical and pharmacokinetic aspects. Furthermore, density functional theory (DFT) was carried out to better understand the structural properties, stability, and chemical reactivity of the most promising derivatives. In summary, this study offers new anticancer candidates with acylhyrazone/hydrazone scaffolds which may need further optimization.

Two significant worldwide health issues that call for the creation of new therapeutic medicines are oxidative stress and antibiotic resistance. Quinazolinone-1,2,4-triazole derivatives, which have a variety of pharmacological characteristics, may be able to help with these problems. As possible antibacterial and anticancer targets, this study sought to synthesized novel quinazoline-4(3H)-one derivatives containing an NH group at position 3 with 1,2,4-triazoles (7a–7k). The chemical structures of all compounds were characterized by NMR (1H/13C), IR and mass spectroscopy. Notably, derivatives 7d and 7e exhibited the greatest MIC values against S. epidermidis, while 7f was the best against S. aureus with MIC of 3.5 μg mL−1, two-fold efficacy more than that was recorded with moxifloxacin. All of the synthesized compounds showed promising anti-proliferative activity, with one compounds 7e having potent cytotoxic activity against MDA-MB-231 cell line (IC50 = 11.80 ± 1.2 μM) and active against MCF-7 (IC50 = 11.80 ± 1.2 μM respectively) in comparison to the reference DXN (IC50 = 9.48 ± 0.6 and 7.12 ± 2.0 μM, respectively). Molecular docking was performed using the protein structure of E. coli Topoisomerase IV, with the interacting effectively with key residues IleA:116, SerA:117, ArgA:93, GluA:46, ThrA:163, and GlyA:71, consistent with their antimicrobial activity. The chemical nature of these compounds was revealed by performing the density functional theory (DFT) calculation using hybrid B3LYP functional with 6-31 g(d) basis set. Additionally, these compounds exhibited promising physicochemical properties, paving the way for discovering new antimicrobial drugs.

The present study reports the synthesis of a nanomagnetic heterogeneous catalyst, namely, Fe3O4@SiO2@Si(CH2)3@melamine@salicylicaldehyde@Cu. This synthesis occurred through intermolecular forces, covalent and dative bonds. After synthesis of the catalyst, its structure was confirmed through different characterization techniques, including FTIR, FESEM, TEM, EDX, VSM, and TGA. In sequence, the activity of the as-synthesized catalyst was evaluated using 4-hydroxycoumarin, malononitrile, and various benzaldehydes as a multi-component model reaction. Then, the reaction condition was optimized to find the solvent type, catalyst amount, and temperature corresponding to ethanol, 0.03 g of catalyst, and reflux conditions. Finally, various derivatives of dihydro-pyrano[3,2-c]chromenes were synthesized using aryl and heterocyclic aldehydes. To evaluate the reuse of the as-synthesized catalyst, it was recovered using an external magnet and used in five cycles. The results showed that the catalyst could be recovered and reused without significant leaching and loss in efficiency. Various characterization techniques confirmed the stability of the used catalyst. Since the magnetic properties of the catalyst allow for easy separation and recycling, maintaining considerable yield for at least five cycles, probably due to the presence of melamine, which plays a vital role in stability and reusability. The present procedure can be done in gram-scale amounts, which can be a candidate for further scaling up.

A novel coumarin-based strapped calix[4]pyrrole, C4P9, was synthesized through an acid cyclization reaction followed by the reaction of coumarin with dipyrromethane. The structure of C4P9 was confirmed using 1H-NMR,13C-NMR, and mass spectrometry. Structural analysis revealed a pre-organized conformation for anion recognition, facilitated by intramolecular hydrogen bonding and the rigid strapping unit. An in-depth investigation of anion binding with various species such as F−, Br−, Cl−, I−, AcO−, NO3 −, HSO4 −, SCN−, and H2PO4 − was conducted using UV-vis and NMR spectroscopy. The anion binding studies were validated by comparing 1H-NMR spectra of free receptor C4P9 with that of C4P9@F. The results from the online supramolecular Bindfit v0.5 program and Job’s plots indicated a 1:1 stoichiometry for the complexation between C4P9 and anions. The coumarin strap enhanced the binding ability and selectivity toward anions, as evidenced by calculations of binding constants. This was observed through interactions such as anion—π (involving aromatic moieties at the meso-position) and C–H—anion (involving the strapped linker and aromatic moiety) as well as N–H—anion interactions. This study demonstrates the potential of coumarin-based strapped calix[4]pyrrole as a versatile platform for developing functional anion receptors, particularly in anion/ion-pair coordination chemistry and supramolecular chemistry in general.

A new series of 5-aryl-3-(4-aryl-1,3-thiazol-2-yl)-1,2-oxazole derivatives 12–27 have been efficiently synthesized from 5-aryl-1,2-oxazole-3-carbothioamides 7a–d and 2-bromo-1-aryl ethanone 8–11. Compounds 12–27 were characterized by IR and NMR spectroscopy and mass spectrometry methods. Compounds 12–27 were evaluated for in vitro antimicrobial activity against P. mirabilis, E. coli, S. aureus, B. subtilis, A. niger and C. albicans strains. Amongst the sixteen derivatives, against the P. mirabilis, compounds 12, 14, 16, 17, 18, 20, 21, 22, 23, 24, 26, and 27 exhibited good activity. The SAR exposed that for the 3,4-dimethoxyphenyl group at the C-5 position of the 1,2-oxazole, all four derivatives 20–23 showed good activity against P. mirabilis, which indicates the 3,4-dimethoxyphenyl group is essential for activity. Against the microbial strains E. coli, B. subtilis, S. aureus, A. niger and C. albicans, compounds 12–27 were found less active. The active derivatives were evaluated for cytotoxicity against normal cell line of mouse embryonic fibroblast cells (3T3L1) at 25 and 50 µg/mL concentrations and found non-cytotoxic. These results suggested that the clubbing of the 2-position of the 1,3-thiazole with the 3-position of 1,2-oxazole is less effective for a broad spectrum of activity and needs further modifications.