Alizarin Red (AR) is one of the most colored hazardous industrial dyes. For effective removal of AR, a new sorbent of modified heterocyclic-magnetite chitosan nanocomposite labeled as AOC@MC was synthesized and characterized by FTIR, TGA, XRD, BET, TEM,SAED pattern and SEM-EDX. Effect of contact time, pH, adsorbent dosage, initial Alizarine Red concentration and temperature was investigated. The maximum AR removal was 98.9% and attained at optimum conditions which were pH = 3.0, contact time = 50 min., and adsorbent dosage = 0.03 g/L. The findings revealed that at pH 3 and 30 °C, the maximum adsorption capacity was approximately 162 mg/g. Within 50 min, equilibrium adsorption was attained. A pseudo-second-order equation might be used to fit the kinetic data that was acquired at the optimal pH level of 3. Langmuir adsorption isotherms could accurately represent the adsorption process. The antimicrobial properties of the functionalized sorbent AOC@MC and its heterocyclic base AOC were characterized by determining the zone of inhibition (ZOI) against Staphylococcus aureus and Klebsiella pneumonia as a model for Gram-positive and Gram-negative bacteria respectively. AOC@MC exhibits promising activity with clear zones of 20.1 ± 0.2 and 17.6 ± 0.4 mm for S. aureus and K. pneumonia respectively. Overall, the modified sorbent AOC@MC was efficient on AR dye removal and antibacterial activity compared to the corresponding heterocyclic compound AOC.

Background: Derivatives of Pyrido[2,3-d]pyrimidine-6-carboxylate are promising multi-target scaffolds. This study focused on synthesizing 16 amino-functionalized derivatives and evaluating their dual anticancer and antibacterial activities, supported by mechanistic and computational analyses. Objectives: Design and synthesize derivatives, evaluate cytotoxicity against HeLa, HepG-2, and MCF-7 (selectivity against WI-38), investigate EGFR^WT and EGFR^T790M inhibition, assess cell cycle, apoptosis, and migration effects, antibacterial efficacy against E. coli and P. aeruginosa, and perform in silico ADMET, docking, molecular dynamics, DFT, and antiviral predictions. Methods: Synthesized 16 derivatives; tested for cytotoxicity, EGFR inhibition, cell cycle, apoptosis, migration; assessed antibacterial activity; performed ADMET profiling, molecular docking, molecular dynamics, and DFT calculations. Results: Derivatives 1, 2, and 7 showed highest cytotoxicity (IC₅₀ = 3.98–17.52 μM; WI-38 IC₅₀ = 64.07–81.65 μM). Compound 1 potently inhibited EGFRWT (IC₅₀ = 0.093 μM) and EGFRT790M (IC₅₀ = 0.174 μM), induced G0/G1 arrest (74.86%) and apoptosis (26.37%), and reduced MCF-7 migration (69.63%). Moderate antibacterial activity observed (MIC = 50 μg/mL). ADMET indicated favorable pharmacokinetics, low CYP inhibition, negative mutagenicity, and oral toxicity class III. Molecular dynamics confirmed stable binding (EGFRWT RMSD 3 Å; EGFRT790M 3.5–4.6 Å) with persistent hydrogen bonds. In silico antiviral evaluation suggested strong binding to HCV NS5A (–9.36 kcal/mol), SARS-CoV-2 Mpro (–9.82 kcal/mol), and E.coli DNA gyrase (–10.25 kcal/mol). Conclusions: Compound 1 exhibits dual anticancer and antibacterial activity, supported by mechanistic and computational analyses, highlighting pyrido[2,3-d]pyrimidines as promising multi-target therapeutic scaffolds.

In response to recent advances in computer-aided drug discovery (CADD) enabled by high-performance computing, computational approaches were employed to support and rationalize the investigation of a VEGFR-2-targeted anticancer candidate, combining molecular-level modeling with experimental validation. Initial in silico ADMET profiling and molecular docking were conducted to support the evaluation of drug-like properties and target engagement within a series of para-toluidine-based derivatives (1–14). The most biologically active compound was further evaluated through 100 ns molecular dynamics simulations and comprehensive DFT calculations to investigate binding stability and electronic characteristics. Based on a rational design strategy and supported by computational analyses, the compounds were synthesized and fully characterized using IR, MS, ¹H/¹³C NMR, and elemental analysis. Biological evaluation was performed against HepG-2, MCF-7, HCT-116, and normal WI-38 cells. Mechanistic studies included VEGFR-2 inhibition, wound-healing migration assays, cell-cycle distribution analysis, apoptosis assessment, and caspase-3 activation. Several derivatives exhibited micromolar cytotoxic activity, with compound 14 emerging as the most active against HepG-2 cells (IC₅₀ = 7.84 ± 0.5 µM), showing cytotoxic activity comparable to that of sorafenib (IC₅₀ = 9.18 ± 0.6 µM) and demonstrating favorable selectivity toward normal WI-38 cells (IC₅₀ = 67.75 ± 3.6 µM). Compound 14 showed moderate VEGFR-2 inhibitory activity (IC₅₀ = 0.55 µM), significant suppression of cell migration, pronounced G₀/G₁ cell-cycle arrest, and robust apoptosis induction supported by caspase-3 activation. Molecular docking and MD simulations supported a stable binding mode within the VEGFR-2 active site. This integrated framework highlights compound 14 as a selectively active VEGFR-2-oriented anticancer candidate scaffold with a favorable selectivity profile, supported by experimental and computational analyses, warranting further lead optimization.

Newly modified magnetic chitosan nanoparticles were synthesized for the high-efficiency removal of cadmium ions from aquatic environments. The structure and morphology of the composites were confirmed using FTIR, TGA, XRD, BET, SEM, TEM, SAED pattern analysis, and zeta potential. Under optimal conditions (pH = 6.0, contact time = 120 min, and sorbent dosage = 0.005 g/100 mL), the maximum removal of Cd (II) by synthesized samples MC, SA, and SB was 90.8%, 95%, and 95.15%, respectively. The kinetic data at optimal pH = 6 could be accurately described using a pseudo-second-order equation, while the Langmuir isotherm model best represented the sorption process. The Langmuir Q_max values for the synthesized nanocomposites S*, S3, S4, S*t, S3t, and S4t were 243.90, 250, 270.27, 212.76, 237.09, and 238.09, respectively. The thermodynamic analysis of these samples shows that the sorption process was exothermic (negative ∆H°) − 15.148, − 13.60, − 13.18, − 18.163, − 16.820, and − 16.06 kJmol⁻¹, respectively. This implies that the diffusion of Cd(II) on the sorbent decreased with the temperature rise. The positive values of ΔS⁰ were 152.37, 147.80, 146.83, 160.94, 157.08, and 154.93 kJmol⁻¹, respectively. The antimicrobial properties of the functionalized sorbents SA and SB were evaluated by measuring the zone of inhibition (ZOI) against Staphylococcus aureus and Klebsiella pneumoniae, representing Gram-negative and Gram-positive bacteria, respectively. SA and SB showed promising activity, demonstrating clear zones of (20 ± 0.2 and 18 ± 0.4 mm), and (22 ± 0.2 and 20 ± 0.4 mm) for S. aureus and K. pneumoniae, respectively. Additionally, these sorbents demonstrated moderate antioxidant activity, with the highest scavenging percentages of 94.20% and 96.63%, respectively, at a concentration of 1000 µg/mL, as assessed by the DPPH method.

Background: Cancer patients are highly susceptible to microbial infections due to immune suppression, necessitating therapeutic strategies that integrate anticancer efficacy with effective antimicrobial intervention. Chalcone-derived nitrogen-fused heterocycles represent a promising platform for developing multi-target agents with relevance to antimicrobial drug delivery, particularly for localized infections. Methods: A series of chalcone-based pyrazoline-thiadiazole nitrogen-fused azole hybrids was synthesized via thiosemicarbohydrazide-functionalized intermediates and fully characterized. Antiproliferative activity was evaluated against MCF-7, HepG-2, HeLa, and HCT-116 cell lines, alongside selectivity toward WI-38 normal fibroblasts. Antibacterial, antibiofilm, and in vivo efficacy were assessed against methicillin-resistant Staphylococcus aureus (MRSA USA300) and Acinetobacter baumannii AB5057. Mechanistic investigations included cell-cycle analysis, apoptosis assays, ERK2, RIPK3, p53, BAX/Bcl-2 quantification, DNA gyrase inhibition, molecular docking, molecular dynamics simulations, and density functional theory calculations. Results: Compound 13 exhibited potent cytotoxicity, particularly against MCF-7 (IC₅₀ = 3.87 ± 0.2 µM), outperforming doxorubicin (IC₅₀ = 4.17 ± 0.2 µM), with high selectivity indices (SI = 10.7 for MCF-7). Mechanistically, compound 13 induced G₂/M arrest (40.16% vs. 14.15% control), increased apoptosis to 32.89%, up-regulated ERK2 (3.17-fold), RIPK3 (11.97-fold), and p53 (3.54-fold), and markedly increased the BAX/Bcl-2 ratio (~42-fold). Compounds 7 and 13 displayed bactericidal activity against MRSA and A. baumannii (MIC/MBC = 10 mg/mL), potent antibiofilm effects, and significant in vivo efficacy in an MRSA skin infection model. Compound 13 reduced bacterial load by ~5 log units, outperforming vancomycin. DNA gyrase inhibition (IC₅₀ = 17.10 ± 0.17 µM) and computational studies supported target engagement. Conclusions: Pyrazoline-thiadiazole-based nitrogen-fused azole hybrids, particularly compound 13, demonstrated quantifiable anticancer and antimicrobial efficacy with strong in vivo validation, supporting their potential as multi-target candidates relevant to antimicrobial drug delivery in infection-prone cancer patients.

Naphthyridine derivatives have emerged as privileged scaffolds with diverse pharmacological activities, particularly in anticancer and antiviral drug discovery. In this study, a series of naphthyridine-based derivatives (1–10b) was designed, synthesized, and structurally characterized using IR, ¹H/¹³C NMR, and mass spectrometry, and evaluated as dual-function antiproliferative and anti-fowlpox virus agents supported by integrated computational analyses. The synthesized compounds were screened for in vitro antiproliferative activity against HeLa, HCT-116, and MCF-7 cancer cell lines, as well as normal WI-38 lung fibroblasts. Several derivatives exhibited potent cytotoxic activity with enhanced selectivity toward cancer cells. Compound 5b showed the highest activity against HeLa cells, compound 1 was most effective against HCT-116 cells, while compounds 7 and 8 displayed remarkable activity against MCF-7 cells, with compound 7 surpassing doxorubicin and compound 8 demonstrating excellent selectivity toward normal cells. Mechanistic investigations revealed that compounds 7 and 8 acted as dual topoisomerase I/IIβ inhibitors, inducing G2/M cell cycle arrest and intrinsic apoptosis associated with caspase-9 activation and downregulation of topoisomerase II protein expression. Selected derivatives were further evaluated for antiviral activity against fowlpox virus using in ovo and in vivo SPF embryonated chicken egg models, where compounds 2 and 9a exhibited the highest therapeutic indices, comparable to ribavirin, and compound 9a markedly suppressed viral replication and titers in vivo. ADMET profiling, molecular docking, molecular dynamics simulations, and DFT calculations supported the experimental findings and identified compound 10a as the most favorable theoretical candidate. Overall, this integrated experimental–computational approach establishes naphthyridine derivatives as a rationally designed multifunctional chemotype for simultaneous anticancer and antiviral drug development.