Two novel pyrazolo[3,4-g]isoquinolines (III and VI) have been synthesized, and their corresponding structures were confirmed using X-ray crystallography. The short intermolecular contacts in the crystals of III and VI were identified through the analysis of the Hirshfeld surface and fingerprint plots. These analyses reveal the involvement of CS, CO, and the amine functional groups in the intermolecular hydrogen bonds and that the major contact is H···H with an overall contribution of 53-57 %. The optimized geometries and the global reactivity properties of both molecules were generated using DFT methods at the PCM-B3LYP/6-31+G(d,p) level of theory. The geometrical parameters of both molecules are relatively well reproduced with correlation coefficients between the experimental and calculated bond lengths, bond angles, and torsion angles in the ranges 90-99 %. Both compounds show similar electronic and molecular properties. Treatment for neurodegenerative and psychiatric illnesses increasingly involves pharmacologically the inhibition of glycogen synthase kinase-3 (GSK-3). Here we have focused on understanding the binding ability of our molecules with GSK-3 using molecular docking. III and VI exhibit strong binding affinity toward the GSK-3 binding site, and they formed stable complexes with their amino acids of free binding energies of 7.8 and -7.1 kcal/mol, respectively. Molecular dynamics studies were performed to investigate the stability of III-GSK-3 and VI-GSK-3 complexes. MD analysis of the RMSD, RMSF, and rGyr plots demonstrate the stability of III and VI within the binding site of GSK-3. ADMET analyses reveal that both compounds may exhibit drug-like properties such as high absorption, polarity, lipophilicity, and oral bioavailability.

Abstract

Nowadays design of multi-functionalized textiles as technical textiles is highly demanded to be applied in different environments and under hard weather condition. Herein, tri-functionalized (fluorescent, antimicrobial and UV-protection) cotton textiles were designed by immobilization of heterocyclic compounds based on quinazoline derivatives (QDs). Firstly, four quinazoline derivatives (QD-1 = H, QD-2 = O–CH₃, QD-3 = Cl, QD-4 = H [without COOH]) were synthesized for the first time starting from 2-(chloromethyl) quinazoline-4(3H)-one. The chemical structure of all obtained QDs were investigated by NMR (¹H & ¹³C) and infrared spectroscopy, in addition to the measurement of melting points, yields and emission spectra. Secondly, the synthesized QDs were immobilized within cotton textile, while cotton was per-activated by interaction with cationic reagent. The modified textiles (QDs@Q-cotton) gained dark yellow color. The QDs@Q-cotton emitted greenish radiation and showed intense emission fluorescence at 485–521 nm. Good–very good (UPF = 23.6–32.8) and good (21.3–25.8) UV protection was respectively shown for QDs@Q-cotton before and after 10 washings. The protection from UV radiation for QDs@Q-cotton is attributed to the reflection of UV radiation by effect of QDs micro particles which deposited within the cotton matrix. The modified textiles exhibited antimicrobial action against S. aureus and E. coli bacteria, while the mortality was 79.9–89.1% and 69.7–76.2% before and after 10 washings, respectively. The antibacterial activity of the QDs@Q-cotton fabrics is attributed to the QDs skeleton. The highest antibacterial action for QD-3@Q-cotton is related to the chlorine derivative. The multi-functionalized textile with good durability could be successfully employed in the military/soldiers clothes.

Heterocyclic compounds, including isoquinoline derivatives with oxygen and sulfur groups, are important in anticancer drug discovery. They show strong biological activity and structural diversity. Medicinal studies, molecular docking, and DFT analysis help understand their effectiveness, binding ability, and stability. For this purpose, we synthesized a new isoquinoline derivative (AHIC). Its structure was verified by single-crystal X-ray analysis. The compound's geometry, FMO, and MEP were analyzed using DFT, supported by experiments. Hirshfeld surface, 3D energy framework, NLO, and NBO analyses identified hydrogen bonds affecting crystal packing. The compound shows strong NLO properties, high charge transfer, and stability, suggesting potential as an anticancer drug. The medicinal potential of AHIC was evaluated through an in silico approach in which it proved to be an effective candidate for anticancer drug development as it efficiently bound with the target substrates with binding energies of −6.87 and −6.31 Kcal/mol along with ligand efficacies of −0.24 and −0.22 Kcal/mol against Tdp1 and EGFR substrates. The MD simulation studies showed the stability of the ligand-protein complexes by calculating the RMSD for the conformation changes in the protein structure over the simulation trajectory and RMSF and SASA parameters for the accessibility of water molecules in the cell-like environment.

This work involves synthesis, characterization, crystal data investigation, Hirshfeld surface analysis, and DFT calculations of a new tatrahydroisoquinoline derivative, namely, 7-Acetyl-4-cyano-1,6-dimethyl-3-ethoxycarbonylmethylthio-6-hydroxy-8-(3-pyridyl)-5,6,7,8-tetrahydroisoquinoline (ACTQ). The crystal structure is determined by single crystal XRD, which showed that O-HO, C-HO, C-HN hydrogen bonding interactions, along with C-Nπ and C-Hπ, participate in the stabilization of the supramolecular assembly. A density functional theory (DFT) study was performed to investigate the electronic and geometric properties of ACTQ in its gaseous state. Geometry optimization revealed that the S–C bonds exhibited the longest bond lengths, whereas the O–H bond was the shortest. The subsequent NBO, QTAIM and NCI analyses showed that a weak intramolecular O-HO hydrogen bond exists in ACTQ. Although NCI also derived from the Bader’s AIM theory, the NCI result showed a difference with respect to the QTAIM result in this study. The ACTQ was subjected to structural activity relationship analysis, based on which GSK-3β was taken, and molecular docking analysis was performed. In addition to this, ADMET was also carried out to understand the future drug candidacy.

Phthalates, including dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), are widely
used plasticizers associated with male reproductive toxicity. This study evaluated the dose- and
temporal-dependent effects of DBP and DEHP (100, 200, and 400 mg/kg for 15 days) on testicular
structure and function in immature Swiss albino mice at 36, 45, 50, and 70 days of age. Biochemical
analyses revealed significant glutathione depletion accompanied by increased nitric oxide and lipid
peroxidation levels, suggesting oxidative imbalance. Histological evaluation demonstrated severe
dose-dependent testicular injury, particularly at 36–45 days, with the 400 mg/kg groups showing 100%
damaged seminiferous tubules and marked reductions in Johnsen’s scores (3.5 ± 0.17 vs. 9.9 ± 0.10 in
controls). Increased Caspase-3 and NF-κB expression suggested possible involvement of apoptotic
and inflammatory responses. Longitudinal assessment from 50 to 70 days revealed a dose-dependent
recovery pattern, with substantial restoration in lower-dose groups, whereas higher doses remained
associated with persistent tubular damage at 70 days (47.0% in DBP and 58.8% in DEHP groups).
These findings suggest that the severity of testicular injury and the extent of recovery are influenced
by phthalate exposure dose. Therefore, further studies are required to fully understand the underlying
molecular mechanisms.

Cadmium (Cd) is a dangerous heavy metal that is non-degradable in the environment. Many organs can accumulate Cd
and adversely affect organ function and health. Cd is considered as a teratogenic and embryotoxic agent. This study aims
to evaluate the teratogenicity of Cd at concentrations lesser than the permissible and its effects on the heart during chick
embryogenesis. Fertilized eggs of the chick Gallus domesticus were divided into; control, saline injected and four experimental
groups injected with single doses of 5, 25, 50 or 75 μM of CdCl2.
Histological observations of the heart before hatching
and the cardiomyocytes after hatching were recorded. Morphometric measurements of heart chambers were achieved at 3,
4 and 6 days of incubation. Electrocardiograph and respiratory rate were recorded at tenth day. Different cardiac problems
had been brought on by Cd. In comparison to controls, the heart looked much larger, and in certain cases, growth retardation
was seen. Degeneration in heart walls and malformations of dorsal aorta were noticed. Morphometrically, the width and wall
thickness of heart chambers showed significant changes. Heart beats and respiratory rate significantly decreased compared to
control. The cardiotoxic effect of Cd on heart compartments structure and function was dose dependent. One of Cd toxicity
is its ability to induce cellular oxidative stress. The heart in particular is sensitive to oxidative stress. Cardiac oxidative stress
might intensify heart failure and promote disease progression. Calcium is one of the components that is needed for normal
heart work. Cd might interfere with calcium metabolism by removing it from the body.