Search Results (305)

Six novel pyrazole-based carbohydrazone derivatives (3a–3f) bearing structurally diverse heteroaromatic substituents were synthesized and characterized by ATR-FTIR, ¹H NMR, APT-¹³C NMR, and HRMS analyses. Their multifunctional bioactivity was evaluated using antioxidant, photoprotective, CT-DNA-associated spectroscopic response, cytotoxicity, and scratch wound closure assays. Antioxidant activity was assessed by DPPH radical scavenging, Fe²⁺ chelation, and ferric thiocyanate (FTC) assays against appropriate reference standards, while photoprotective potential was determined by spectrophotometric SPF analysis using carrot seed oil as a reference. The benzothiazole-containing derivative (3f) showed the strongest DPPH scavenging activity, FTC antioxidant capacity, and photoprotective activity, while also producing one of the most pronounced CT-DNA-associated spectroscopic responses under the experimental conditions employed. In contrast, the benzimidazole derivative (3e) displayed the highest Fe²⁺ chelating activity among the synthesized compounds. In cell-based assays, the imidazole- and thiazole-containing derivatives (3b and 3c) showed the most favorable balance between growth-inhibitory potency and selectivity toward A431 epidermoid carcinoma cells relative to HaCaT keratinocytes. Scratch assay results did not support direct anti-migratory activity under the tested conditions but indicated compound-dependent modulation of wound-closure-associated cellular responses. Overall, these findings demonstrate that heteroaromatic substitution strongly modulates redox behavior, CT-DNA-associated spectroscopic behavior, photophysical properties, and cytotoxic selectivity in pyrazole-based carbohydrazones, identifying this scaffold as a structurally tunable platform for further bioactivity optimization. Full article

The introduction of amine groups into the four-membered central ring of squaraine dyes is expected to enhance the intrinsic cytotoxicity of this scaffold. In this study, the biological effects of eight benzothiazole-based aminosquaraine dyes were investigated by varying the length of the N-alkyl chains and the nature of the introduced amine. Biological activity was evaluated through different assays in several cell lines, including apoptosis and cell cycle analysis, as well as confocal microscopy studies. Overall, the incorporation of amino, methylamino, and ethanolamino groups significantly increased cytotoxicity, with the corresponding dyes displaying low half-maximal inhibitory concentration values, in some cases even lower than that of the positive control, 5-fluorouracil. In contrast, derivatives bearing diethanolamino or ethylenediamino groups exhibited lower cytotoxicity, particularly the dye containing N-decyl chain. For the dyes selected for further investigation, bearing a methylamino group and N-butyl or -hexyl chains, the induction of apoptosis was evident, especially for methylaminosquaraine dye 3. These dyes also exhibited antiproliferative effects, as evidenced by their ability to induce cell cycle arrest. Confocal microscopy revealed a predominantly cytoplasmic distribution, likely associated with cytoplasmic organelles, with limited penetration into the nucleus. Overall, although squaraines are widely recognized as promising photodynamic agents, the present results suggest that they may also be explored in chemotherapeutic approaches, particularly when exhibiting high intrinsic cytotoxicity. Full article

UVA exposure elicits immediate and persistent pigment darkening of the skin, which is thought to result from the oxidation and polymerization of existing melanin and/or precursors. Melanocytes produce eumelanin and pheomelanin. Eumelanin consists of 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA), while pheomelanin consists of benzothiazine and benzothiazole units. Melanins can be analyzed by quantifying specific degradation products using HPLC. Specifically, eumelanin can be analyzed as pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3-dicarboxylic acid (PDCA), specific degradation products of DHICA and DHI, respectively. Benzothiazole pheomelanin can be analyzed as thiazole-2,4,5-tricarboxylic acid (TTCA), whereas benzothiazine pheomelanin is analyzed as 4-amino-3-hydroxyphenylalanine (4-AHP) and 3-amino-4-hydroxyphenylalanine (3-AHP). Upon UVA exposure, melanins undergo structural modifications. Eumelanin undergoes oxidative cleavage to free pyrrole-2,3,5-tricarboxylic acid (Free PTCA) and undergoes cross-linking to form pyrrole-2,3,4,5-tetracarboxylic acid (PTeCA). UVA exposure of pheomelanin induces oxidative conversion from the benzothiazine to the benzothiazole. Nevertheless, these structural modifications have never been previously characterized in human skin. In this study, we exposed ex vivo skin to increasing UVA1 doses (60, 90 and 120 J/cm²; n = 6 in triplicate) and characterized the induced pigment darkening before, immediately, and 2 h after exposure through colorimetry, HPLC and spectrophotometry. The results showed changes in the CIELAB colorimetric parameters, namely a decrease in Luminance L*, the yellow-blue component b* and the Individual Typology Angle (ITA) in UVA1-exposed samples, indicative of skin darkening. In parallel, UVA1 exposure induced significant modifications of the levels of absorbance at 500 nm (A500) and melanin markers PTCA, PTeCA, PDCA, TTCA, and 4-AHP, as well as in the ratios of various markers, such as PTeCA/PTCA, Free/Total PTCA, and TTCA/4-AHP, indicative of photooxidation/degradation of melanins. Our study provides the first evidence of UVA1-induced modifications of melanins associated with pigment darkening occurring in human skin. Full article

Consumer preferences for pork are increasingly prioritizing quality traits such as flavor and tenderness, which are often superior in Chinese indigenous pig breeds. The primary objective of this study was to explore the molecular basis of flavor traits using Rongchang (RR), Yorkshire (YY), and RR × YY (YR) breeds. The investigation focused on meat quality traits, along with untargeted metabolomics, lipidomics, and volatile flavor compound (VOC) profiling of the longissimus dorsi muscle. The results indicated that RR pork exhibited higher pH levels and overall acceptability. Analyses using electronic nose and tongue demonstrated that RR pork elicited stronger responses for W2S, W1S, and W1C sensors, as well as for umami and sourness. A total of 15 VOCs were identified as differing among the breeds. RR pork contained higher levels of benzothiazole and dimethyl sulfoxide, but lower levels of nonane, 2-methylheptane, and 2,4-dimethylheptane. Metabolomic analysis revealed 45 distinct metabolites, with a greater abundance of flavor precursors such as α-ketoglutaric acid in RR pork. Lipidomic analysis identified 22 different lipids, with triglycerides being more enriched in RR pork. Phospholipids, such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE), varied by breed, with PC (e) being lowest and cardiolipin highest in RR pork. Correlation network analysis revealed that nonane, 2-methylheptane was the most connected flavor compound, positively correlating with certain lipids and metabolites, such as PC (18:1_18:1), PE (18:2e_22:6), PC (36:4) and 2-phenylglycine, and negatively correlating with PC (32:0e), SM (d41:1), N-hydroxy-2-acetamidofluorene, and histamine. This multi-omics approach provides a comprehensive view of the molecular signatures associated with pork preference, identifying potential biomarkers for meat quality that can be leveraged for future breeding strategies. Full article

The cigarette beetle, Lasioderma serricorne, is a globally important pest of stored products, and prolonged fumigant use has accelerated resistance development. Glutathione S-transferases (GSTs) are key phase II detoxification enzymes that mediate insect tolerance to xenobiotics. In this study, we identified nine GST genes (LsGSTs) in L. serricorne and classified them into four cytosolic classes, namely epsilon, delta, theta, and sigma, based on phylogenetic analysis. Most LsGSTs were predominantly expressed during larval stages, while LsGSTs7 showed peak expression in adults. Tissue-specific profiling revealed predominant expression in metabolically active organs, including the fat body, Malpighian tubules, and midgut. Inhibition of GST activity using diethyl maleate (DEM) significantly increased larval susceptibility to three emerging fumigants: ethyl formate, benzothiazole, and methyl isothiocyanate. Exposure to LC₃₀ and LC₅₀ concentrations of these fumigants induced up-regulation of multiple LsGSTs, highlighting fumigant-specific detoxification responses. RNA interference targeting nine fumigant-inducible LsGSTs markedly elevated mortality and decreased total GST activity under fumigant stress. Furthermore, recombinant LsGSTs6 protein effectively metabolized methyl isothiocyanate, confirming their direct role in fumigant detoxification. Collectively, these findings provide novel insights into the molecular mechanisms underlying GST-mediated tolerance in L. serricorne and identify specific GST isoenzymes as promising molecular targets for innovative resistance management strategies in stored-product pest control. Full article

New benzazole–sesamol derivatives 6a–8c were synthesized via an easily accessible reaction based on the coupling of Sesamol with in situ generated electrophilic N-alkoxycarbonylbenzazolium ions. This strategy successfully integrated benzothiazole, benzimidazole, and 5,6-dimethylbenzimidazole fragments with the biologically active natural lignan Sesamol. The structural integrity and the specific position of the newly formed C–C bond was confirmed by ¹H-, ¹³C{¹H}-, HSQC-NMR, FTIR, and HRMS analyses. The obtained compounds with yields in the range of 71–95% were evaluated for their in vitro radical scavenging activity and subjected to in silico predictions of mutagenicity and toxicity. Radical scavenging activity studies demonstrate that the introduction of a benzothiazoline ring (compounds 6a and 6b) enhances radical scavenging activity compared to Sesamol in the DPPH assay, outperforming the benzimidazole analogues. In silico analyses identified compounds 7b, 7c, 8a, 8b, and 8c as promising molecules due to the absence of mutagenic and irritant effects and their low toxicity profiles. In particular, compounds 7a, 7b, and 8a were found to be significantly safer than Sesamol. Compound 7a exhibited the highest safety profile, characterized by an LD₅₀ value of 3046.92 mg/kg. Full article

The search for new growth-regulating compounds remains a relevant research direction in view of the issue of food security. Previously, a number of thiazolyl acetic acid derivatives have been synthesized, which are promising biologically active compounds according to their physicochemical characteristics. The aim of this work was to study the growth-regulating properties of both previously and newly synthesized thiazolyl acetic acid derivatives using a growth phytotest with Lepidium sativum and Sinapis alba. This study was carried out under laboratory conditions of phytotesting growth indicators of test plants of the class Dicotyledones—L. sativum and S. alba under the influence of 10 μg/mL, 100 μg/mL, and 1000 μg/mL aqueous solutions of the compounds with a comparative analysis of the action of the active components of Rhizopon^TM and herbicide benazolin. It was found that, exhibiting high herbicidal properties at a concentration of 1000 μg/mL (primarily the compound with a benzothiazole fragment), the studied thiazolyl acetic acid derivatives with decreasing concentration (100 μg/mL and 10 μg/mL) reduce phytotoxicity to its complete elimination against L. sativum and S. alba for the compound 2-[2-(N-tert-butoxycarbonyl)-aminoethyl-1,3thiazol-4-yl]acetic acid (compound 3), as well as against L. sativum for the compound 5-phenylthiazol-2-yl acetic acid (compound 5). A weak stimulating effect on the length of the above-ground part of S. alba seedlings was recorded for 2-[2-(3,3,3-trifluoropropyl)-1,3thiazol-4-yl]acetic acid (compound 1) and 2-[2-(N-tert-butoxycarbonyl)-aminoethyl-1,3thiazol-4-yl]acetic acid (compound 3) at their concentration of 10 μg/mL; however, an improvement in the vitality index under the action of these compounds was not observed. The results obtained in this study indicate the biological activity of both previously and newly synthesized thiazolyl acetic acid derivatives, namely their growth-regulatory properties, expanding knowledge about promising herbicidal compounds with a possible hormetic effect, which requires further research. Full article

A novel series of benzothiazole scaffolds were presented to test their in vitro α-amylase and α-glucosidase activities for combating diabetes mellitus, which is one of the most rapidly growing diseases. The tested compounds were elucidated structurally by various spectroscopic techniques like ¹H NMR, ¹³C NMR and HRMS. All compounds exhibited a varied range of inhibitory activities against targeted α-amylase and α-glucosidase enzymes, with IC₅₀ values of 1.58 ± 1.20 to 7.54 ± 3.60 µM (α-amylase) and 2.10 ± 1.10 to 8.90 ± 4.10 (α-glucosidase), respectively. The obtained results were compared with the standard acarbose drug, with IC₅₀ values of 0.91 ± 0.20 µM (α-amylase) and 1.80 ± 1.10 µM (α-glucosidase). Specifically, methyl 2-amino-4-((6-methoxypyridin-3-yl)methoxy)benzo[d]thiazole-6-carboxylate (5c) and methyl 4-((6-methoxypyridin-3-yl)methoxy)-2-(thiazole-2-carboxamido)benzo[d]thiazole-6-carboxylate (6b) emerged as potent inhibitors of α-amylase and α-glucosidase enzymes. These potent compounds were further screened for in silico molecular docking studies to investigate possible binding interactions with active sites of targeted enzymes, and results obtained demonstrated that potent compounds exhibited stronger binding affinities toward anti-diabetic enzymes compared to the positive control acarbose. Full article

The paper focuses on the synthesis and characterization of the spectroscopic and electrochemical properties of novel oxime esters. Six benzothiazole-based compounds were synthesized using a simple three-step procedure. The chemical structure of novel oxime esters was confirmed by Nuclear Magnetic Resonance spectroscopy (¹H and ¹³C NMR), as well as FT-IR spectroscopy and elemental analysis. The melting point of these compounds was also determined. The spectroscopic properties were studied in 10 solvents with different polarity. The fluorescence quantum yield was determined using Coumarin I as a reference. Additionally, the E_0→0 transition energy was determined. The electrochemical properties were determined using cyclic voltammetry. To justify their use as potential photoinitiators, preliminary studies were conducted to assess their utility in initiating light-induced polymerization. Based on the results, the proposed oxime esters are potential Type I photoinitiators for free radical polymerization. Full article

Resistance to imatinib remains a therapeutic challenge, largely driven by point mutations within the kinase domain of the BCR-ABL, among which the T315I substitution constitutes the most clinically significant barrier. Ponatinib effectively inhibits this mutant form but is limited by dose-dependent cardiovascular toxicity, prompting efforts to develop safer and more selective agents. Recent advances highlight aminopyrimidine-derived scaffolds and their evolution into thienopyrimidines, oxadiazoles, and pyrazines with improved activity against BCR-ABL^T315I. Further progress has been achieved with benzothiazole–picolinamide hybrids incorporating a urea-based pharmacophore, which benefit from strategic hinge-region substitutions and phenyl linkers that enhance potency. Parallel research into dual-mechanism inhibitors, including Aurora and p38 kinase modulators, demonstrates additional opportunities for overcoming resistance. Combination strategies, such as vorinostat with ponatinib, provide complementary therapeutic avenues. Natural-product-inspired approaches utilizing fungal metabolites provided structurally diverse scaffolds that could engage sterically constrained mutant kinases. Hybrid molecules derived from approved TKIs, including GNF-7, olverembatinib, and HG-7-85-01, exemplify rational design trends that balance efficacy with improved safety. Molecular modeling continues to deepen understanding of ligand engagement within the T315I-mutated active site, supporting the development of next-generation inhibitors. In this review, we summarized recent progress in the design, optimization, and biological evaluation of small molecules targeting the BCR-ABL^T315I mutation. Full article

Azole selenoureas exhibit diverse biological functions. However, the synthesis and biological activity of benzothiazole and benzoxazole selenones remained unexplored. Herein, we report the base-catalyzed synthesis of N-difluoromethyl benzothiazole (or benzoxazole) selenone derivatives, which demonstrated significant antifungal efficacy against Rhizoctonia solani, Phytophthora infestans, Botrytis cinerea, and Fusarium oxysporum. Compound 3b exhibited exceptional antifungal activity against R. solani, with an EC₅₀ of 2.10 mg/L. Moreover, it substantially inhibited sclerotia germination (81.5% at 9 mg/L) and formation (79.3% at 9 mg/L), surpassing octhilinone. The protective effect on detached rice leaves and rice seedlings was found to be 43.4% and 85.2% at 100 mg/L, respectively, and 64.4% and 89.4% at 200 mg/L. These findings suggest that benzothiazole and benzoxazole selenones represent promising lead compounds for sustainable plant disease management. Full article

In the third edition of this Special Issue, the participating researchers focused their studies on bispecific antibodies against solid tumors [contribution 1], teratoma development [contribution 2], the seminoma microenvironment [contribution 3], neuroblastoma and peptidergic systems [contribution 4], hepatocellular carcinoma [contribution 5], the synthesis of novel podophyllotoxin–benzothiazole congeners for use as anticancer agents [contribution 6], the effects of podophyllotoxin derivatives on non-cancerous diseases [contribution 7], and the involvement of the aryl hydrocarbon receptor and the signal transducer and activator of transcription 3 in chemical carcinogenesis [contribution 8] [...] Full article

In the present study, (E)-1-(2-(pyridin-2-yl)benzo[d]thiazol-6-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (4) was designed and synthesized via a three-step reaction sequence. Initially, 6-acetylbenzo[d]thiazol-2(3H)-one (1) was hydrolyzed to the corresponding 5-acetyl-2-aminothiophenol 2 and then cyclized with pyridine-2-carbaldehyde. The final product was synthesized by a base-catalyzed aldol condensation of 1-(2-(pyridin-2-yl)benzo[d]thiazol-6-yl)ethan-1-one (3) and 3,4,5-trimethoxybenzaldehyde and was comprehensively characterized. Full article

The dysregulation of CK1 isoforms is linked to various types of diseases, including neurodegeneration and different types of neoplasia such as colon, pancreatic, breast, and ovarian cancer. For CK1 isoforms, a plethora of effective small molecule inhibitors are available. However, only a few degraders of CK1α and, more recently, proteolysis targeting chimeras (PROTACs) for CK1δ/CK1ε have been reported. In this study, we applied the PROTAC concept by harnessing molecular modelling to design and synthesize a series of candidate CK1δ-targeting PROTACs based on a highly specific and potent benzothiazole-based CK1δ inhibitor that we previously developed in our lab. In the present study, we established a modular synthetic platform to systematically generate a set of PROTAC degrader candidates consisting of the CK1δ-specific inhibitor scaffold, alkyl and PEG linker motifs with various lengths, and Cereblon (CRBN)-engaging pomalidomide and thalidomide derivatives as E3 ligase binders. We demonstrate that several PROTACs degrade CK1δ/ε in various cells. The most potent PROTAC P1d inhibits the phosphorylation of downstream substrates through CK1δ/ε degradation. We establish the requirement of CUL4A^CRBN and the proteasome for the P1d-mediated degradation of CK1δ/ε. Full article

This study reports the solvent-free mechanochemical synthesis of a novel series of 2-hydrazone-bridged benzothiazole derivatives 19–52 via the reaction of 2-hydrazinylbenzothiazole derivatives 4–6 with O-alkylated benzaldehydes 7–18. The stereostructure of the E-isomers was confirmed by 2D NOESY spectroscopy. The antiproliferative potential of these newly prepared 2-hydrazone derivatives of benzothiazole 19–52 was evaluated in vitro against eight human cancer cell lines. Several compounds demonstrated low micromolar IC₅₀ values, with some outperforming the reference drug etoposide. Among the most potent compounds, the 6-chloro-2-hydrazone(3-fluorophenyl)benzothiazole derivative 38 exhibited remarkable activity against pancreatic adenocarcinoma (Capan-1, IC₅₀ = 0.6 µM) and non-small cell lung cancer (NCI-H460, IC₅₀ = 0.9 µM). Structure–activity relationship analysis revealed that derivatives 45–52, featuring a methoxy group at position 6 of the benzothiazole ring and either a methoxy or fluorine substituent at position 3 of the phenyl ring, showed consistently strong antiproliferative effects across all tested cell lines (IC₅₀ = 1.3–12.8 µM). Furthermore, compounds bearing N,N-diethylamino or N,N-dimethylamino groups at position 4 of the phenyl ring generally exhibited superior activity compared to those with morpholine or piperidine moieties. However, as this study represents an initial screening, further mechanistic investigations are required to confirm specific anticancer pathways and therapeutic relevance. In addition to their in vitro anticancer properties, the antibacterial activity of the compounds was assessed against both Gram-positive and Gram-negative bacteria. Notably, compound 37 demonstrated selective antibacterial activity against Pseudomonas aeruginosa (MIC = 4 µg/mL). Overall, this work highlights the efficiency of a green, mechanochemical approach for synthesizing E-isomer hydrazone-bridged benzothiazoles and underscores their potential as promising scaffolds for the development of potent antiproliferative agents. Full article