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Regarding the increased incidence and high mortality rate of malignant melanoma, practical early-detection methods are essential to improve patients’ clinical outcomes. In this study, we successfully prepared novel picolinamide–benzamide (18F-FPABZA) and nicotinamide–benzamide (18F-FNABZA) conjugates and determined their biological characteristics. The radiochemical yields of 18F-FPABZA and 18F-FNABZA were 26 ± 5% and 1 ± 0.5%, respectively. 18F-FPABZA was more lipophilic (log P = 1.48) than 18F-FNABZA (log P = 0.68). The cellular uptake of 18F-FPABZA in melanotic B16F10 cells was relatively higher than that of 18F-FNABZA at 15 min post-incubation. However, both radiotracers did not retain in amelanotic A375 cells. The tumor-to-muscle ratios of 18F-FPABZA-injected B16F10 tumor-bearing mice increased from 7.6 ± 0.4 at 15 min post-injection (p.i.) to 27.5 ± 16.6 at 3 h p.i., while those administered with 18F-FNABZA did not show a similarly dramatic increase throughout the experimental period. The results obtained from biodistribution studies were consistent with those derived from microPET imaging. This study demonstrated that 18F-FPABZA is a promising melanin-targeting positron emission tomography (PET) probe for melanotic melanoma.

Central nervous system (CNS) disorders such as neurodegenerative diseases, multiple sclerosis, or even brain ischemia represent major therapeutic challenges with limited effective treatments. The sigma-1 receptor (S1R), a unique ligand-operated molecular chaperone enriched at mitochondria-associated membranes, has emerged as a promising drug target due to its role in neuroprotection and neuroinflammation. Building upon our previously identified S1R ligand (compound 1), we designed and synthesized six novel benzamide derivatives through pharmacomodulation to optimize affinity, selectivity, and safety profiles. Among these, compound 2 demonstrated superior S1R affinity, improved selectivity over the sigma-2 receptor (S2R), and favorable ADME properties, including enhanced permeability and markedly reduced in vitro cardiac toxicity compared to the lead compound. Functional assays confirmed the agonist activity of key derivatives, while safety evaluations revealed low cytotoxicity and minimal off-target receptor interactions. Collectively, these findings support compound 2 as a promising candidate for further preclinical development in S1R-related CNS disorders.

Malignant melanoma has one of the highest mortality rates of any cancer because of its aggressive nature and high metastatic potential. Clinical staging of the disease at the time of diagnosis is very important for the prognosis and outcome of melanoma treatment. In this study, we designed and synthesized the 18F-labeled pyridine-based benzamide derivatives N-(2-(dimethylamino)ethyl)-5-[18F]fluoropicolinamide ([18F]DMPY2) and N-(2-(dimethylamino)ethyl)-6-[18F]fluoronicotinamide ([18F]DMPY3) to detect primary and metastatic melanoma at an early stage and evaluated their performance in this task. [18F]DMPY2 and [18F]DMPY3 were synthesized by direct radio-fluorination of the bromo precursor, and radiochemical yields were ∼15–20%. Cell uptakes of [18F]DMPY2 and [18F]DMPY3 were >103- fold and 18-fold higher, respectively, in B16F10 (mouse melanoma) cells than in negative control cells. Biodistribution studies revealed strong tumor uptake and retention of [18F]DMPY2 (24.8% injected dose per gram of tissue [ID/g] at 60 min) and [18F]DMPY3 (11.7%ID/g at 60 min) in B16F10 xenografts. MicroPET imaging of both agents demonstrated strong tumoral uptake/retention and rapid washout, resulting in excellent tumor-to-background contrast in B16F10 xenografts. In particular, [18F]DMPY2 clearly visualized almost all metastatic lesions in lung and lymph nodes, with excellent image quality. [18F] DMPY2 demonstrated a significantly higher tumor-to-liver ratio than [18F]fluorodeoxyglucose ([18F]FDG) and the previously reported benzamide tracers N-[2-(diethylamino)-ethyl]-5-[18F]fluoropicolinamide ([18F]P3BZA) and N-[2-(diethylamino)-ethyl]-4-[18F]fluorobenzamide ([18F]FBZA) in B16F10-bearing or SK-MEL-3 (human melanoma)-bearing mice. In conclusion, [18F]DMPY2 might have strong potential for the diagnosis of early stage primary and metastatic melanoma using positron emission tomography (PET).

In this study, a series of 4-[(quinolin-4-yl)amino]benzamide derivatives as the novel anti-influenza agents were designed and synthesized. Cytotoxicity assay, cytopathic effect assay and plaque inhibition assay were performed to evaluate the anti-influenza virus A/WSN/33 (H1N1) activity of the target compounds. The target compound G07 demonstrated significant anti-influenza virus A/WSN/33 (H1N1) activity both in cytopathic effect assay (EC50 = 11.38 ± 1.89 µM) and plaque inhibition assay (IC50 = 0.23 ± 0.15 µM). G07 also exhibited significant anti-influenza virus activities against other three different influenza virus strains A/PR/8 (H1N1), A/HK/68 (H3N2) and influenza B virus. According to the result of ribonucleoprotein reconstitution assay, G07 could interact well with ribonucleoprotein with an inhibition rate of 80.65% at 100 µM. Furthermore, G07 exhibited significant activity target PA−PB1 subunit of RNA polymerase according to the PA−PB1 inhibitory activity prediction by the best pharmacophore Hypo1. In addition, G07 was well drug-likeness based on the results of Lipinski’s rule and ADMET prediction. All the results proved that 4-[(quinolin-4-yl)amino]benzamide derivatives could generate potential candidates in discovery of anti-influenza virus agents.

A library of N -benzylbenzamide, N -phenethylbenzamide and N -benzyloxybenzamide derivatives were designed, synthesized and evaluated as amyloid beta (Aβ42) aggregation inhibitors. These compounds were designed by replacing the α,β-unsaturated linker region of chalcone with an amide bioisostere. The Aβ42 aggregation inhibition properties of these 27 benzamide derivatives were evaluated by the thioflavin T (ThT)-based fluorescence aggregation kinetics assay, transmission electron microscopy (TEM) studies, Aβ42-induced cytotoxicity assay in mouse hippocampal neuronal HT22 cell lines, fluorescence live cell imaging, and computational modelling studies using a pentamer model of Aβ42. These studies led to the identification of N -benzylbenzamides 3a and 3f , N -phenethylbenzamide 5a and N -benzyloxybenzamide 7a as promising compounds that were able to exhibit anti-aggregation properties in the ThT-based fluorescence experiments, TEM studies and more significantly were able to rescue the hippocampal neuronal HT22 cells from Aβ42-induced cytotoxicity (91–96% cell viability at 25 µM). These results demonstrate the usefulness of these benzamide-based templates in the design and development of novel small molecules as chemical tools and therapeutics to study and treat Alzheimer’s disease.

We used a new descriptor called the Klopman index in our software of the “molecular comparative electron topology” (MCET) method to reduce the uncertainty resulting from the descriptors used in QSAR studies. The 3D pharmacophore model (3D-PhaM), which can demonstrate three-dimensional interaction between the ligand -receptor (L-R), is only possible with local reactive descriptors (LRD). The Klopman index, containing both Coulombic and frontier orbital and interactions of atoms of the ligand, is a good LRD. Molecular conformers having the best matching atoms with the template conformer can be selected as one of the most suitable spatial structures for interaction with the receptor, and the LRD values of the atoms in this conformer serve to determine 3D-PhaM. The 3D-PhaM of the N-benzyl benzamide derivatives, such as the melanogenesis inhibitor, was determined by ligand-based MCET and confirmed by the structure-based FlexX docking method. For compounds of the training set (42) and the external cross validation test set (6), the Q 2 (0.862) and R 2 (0.913) of the statistical parameters were calculated, respectively, and were checked by r m 2 (0.85) of the stringent validation.

2-Benzoylamino-N-phenyl-benzamide derivatives (5a–h) were prepared from 2-phenyl-3,1-(4H)-benzoxazin-4-one 3 and substituted anilines 4a–h in the presence of a Keggin-type heteropolyacids series (H3PW12O40·13H2O; H4SiW12O40·13H2O; H4SiMo12O40·13H2O; and H3PMo12O40·13H2O) as catalysts without solvent and under microwave irradiation. We found that the use of H3PW12O40·13H2O acid coupled to microwave irradiation allowed obtaining a high-yielding reaction with a short time. The compound structures were established by 1H-NMR and 13C-NMR. The antibacterial and antifungal activities of the synthesized compounds exhibited an inhibition of the growth of bacteria and fungi.

According to the obtained information from X-ray crystallography, it has been characterized that two distinct parts are observable in the active site of AChE. [...]the ethylacetate was evaporated using rotary evaporator apparatus and obtained precipitate was treated with nhexane and diethyl ether. According to the above mentioned information, all electron withdrawing groups such as Cl, F and nitro caused a remarkable and favorable increase in enzyme inhibitory activity. [...]more conformations could be considered for it to match the receptor.

A series of benzamide derivatives such as 1-(1,3-benzodioxol-5-ylcarbonyl) piperidine (1-BCP) were synthesized by the reaction of substituted benzoic acids with piperidine, morpholine or pyrrolidine using a novel method. The crystals of these benzamide derivatives were obtained by recrystallization. Structures of target and intermediate compounds were determined via FT-IR, 1H-NMR and elemental analysis and X-ray crystallography of select examples. The crystal structures of these compounds have potential applications to identify the binding site for allosteric modulators of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor. The anti-fatigue effects of the benzamide derivatives in weight-loaded forced swimming mice were investigated in a swimming endurance capacity test used as an indicator of fatigue. The swimming times to exhaustion were longer in the b3, d3, and e3 groups than in the caffeine group (p < 0.05). In conclusion, b3, d3 and e3 enhanced the forced swimming capacity of mice. The mechanism of the anti-fatigue effects will be studied in the future.

A high antibotulinal activity of benzamide injected for prevention and of 3-N-butyrylamino-benzamide injected for treatment was observed in mice with intoxication caused by type A botulin toxin. 3-aminobenzamide and 3-N-butyrylaminobenzamide did not inhibit botulinal toxinin vitro.