Search Results (11)

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

Diarrhea remains one of the leading causes of mortality worldwide, especially among children. Accumulated evidence has shown that Shigella species are the most prevalent bacteria responsible for diarrhea in developing countries. Antimicrobial therapy is necessary for Shigella infections; however, the development of resistance against current drugs justifies the pressing need to search for alternative medications. In this study, we have applied antibacterial phenotypic screening to identify potent anti-Shigella compounds across a broad chemical diversity, including selected acetaminophen derivatives containing a benzothiazole backbone, and their combination with certain antibiotics. As a result, two acetaminophen derivatives containing a benzothiazole backbone (4a and 4b) inhibited the growth of Shigella flexneri with a common MIC value of 12.5 µg/mL. These compounds were established through a time-kill kinetics study to be potentially bactericidal. Meanwhile, the 2-aminobenzothiazoles (1a and 1b) used for the synthesis of compounds 4 (a and b) were found to be poorly active (MIC: 100 µg/mL) against this pathogen. Combination studies of 4a and 4b with the least effective antibiotics (ceftriaxone and cotrimoxazole) demonstrated synergistic anti-Shigella activity with MIC values decreasing from 12.5 to 0.781 μg/ mL. The present study demonstrates that the azobenzothiazole dyes 4 (a and b) can be repurposed as potential anti-Shigella compounds, thus providing potential chemical pharmacophores for the discovery of drugs against infectious diarrhea caused by Shigella and other enteric pathogens, especially in developing countries. Full article

The benzothiazole nucleus is a major heterocyclic scaffold whose therapeutic potential has been thoroughly explored due to its structural simplicity and ease of synthesis. In fact, several benzothiazole derivatives have been synthesized over time, demonstrating numerous pharmacological properties such as anticancer, antimicrobial, anti-inflammatory, and antioxidant activities. Herein, we propose a new series of benzothiazole-phthalimide hybrids obtained by linking the phthalimide moiety to differently substituted benzothiazole nuclei through the N atom. These compounds have been screened for their anticancer properties against two human breast cancer cell lines. Furthermore, we delved into the mechanism of action of the most active hybrid, compound 3h, by assessing its capability to damage the nuclear DNA, trigger the apoptotic process in the high metastatic MDA-MB-231 cells, and prevent cellular migration. Moreover, in view of the documented antimicrobial activities of the two scaffolds involved, we explored the antibacterial and antifungal effects of the studied compounds by means of the broth microdilution method. Among the studied compounds, 3h showed the highest antimicrobial activity, both against gram-positive and gram-negative bacterial strains belonging to the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and against fungal strains of the Candida species with MIC_s values ranging from 16 to 32 µg/mL. Full article

The drug-resistance problem is widely spread and becoming more common in community-acquired and nosocomial strains of bacteria. Therefore, finding new antimicrobial agents remains an important drug target. From this perspective, new derivatives of benzothiazole were synthesized and evaluated for their antimicrobial activity and ability to inhibit the DHPS enzyme. The synthesis was carried out by the reaction of benzothiazole N-arylsulphonylhydrazone with N-aryl-2-cyano-3-(dimethylamino)acrylamide, N-aryl-3-(dimethylamino)prop-2-en-1-one, arylaldehydes or diazonium salt of arylamine derivatives, which led to the formation of N-arylsulfonylpyridones 6a–d (yield 60–70%) and 12a–c (yield 50–60%),N-(2-(benzo[d]thiazole-2-yl)-3-arylacryloyl-4-methylsulfonohydrazide 14a–c (yield 60–65%), 4-(benzo[d]thiazole-2-yl)-5-aryl-1H-pyrazol-3(2H)-one 16a–c (yield 65–75%), and N′-(2-(benzo[d]thiazol-2-yl)-2-(2-arylhydrazono)acetyl)-4-arylsulfonohydrazide 19a–e (yield 85–70%). The antimicrobial evaluations resulted into a variety of microbial activities against the tested strains. Most compounds showed antimicrobial activity against S. aureus with an MIC range of 0.025 to 2.609 mM. The most active compound, 16c, exhibited superior activity against the S. aureus strain with an of MIC 0.025 mM among all tested compounds, outperforming both standard drugs ampicillin and sulfadiazine. The physicochemical–pharmacokinetic properties of the synthesized compounds were studied, and it was discovered that some compounds do not violate rule of five and have good bioavailability and drug-likeness scores. The five antimicrobial potent compounds with good physicochemical–pharmacokinetic properties were then examined for their inhibition of DHPS enzyme. According to the finding, three compounds, 16a–c, had IC₅₀ values comparable to the standard drug and revealed that compound 16b was the most active compound with an IC₅₀ value of 7.85 μg/mL, which is comparable to that of sulfadiazine (standard drug) with an IC₅₀ value of 7.13 μg/mL. A docking study was performed to better understand the interaction of potent compounds with the binding sites of the DHPS enzyme, which revealed that compounds 16a–c are linked by two arene-H interactions with Lys220 within the PABA pocket. Full article

In this manuscript, we describe the design, preparation, and studies of antimicrobial activity of a series of novel heteroarylated benzothiazoles. A molecular hybridization approach was used for the designing compounds. The in vitro evaluation exposed that these compounds showed moderate antibacterial activity. Compound 2j was found to be the most potent (MIC/MBC at 0.23–0.94 mg/mL and 0.47–1.88 mg/mL) On the other hand, compounds showed good antifungal activity (MIC/MFC at 0.06–0.47 and 0.11–0.94 mg/mL respectively) with 2d being the most active one. The docking studies revealed that inhibition of E. coli MurB and 14-lanosterol demethylase probably represent the mechanism of antibacterial and antifungal activities. Full article

Based on some homodrimane carboxylic acids and their acyl chlorides, a series of fourteen 2-homodrimenyl-1,3-benzothiazoles, N-homodrimenoyl-2-amino-1,3-benzothiazoles, 4′-methyl-homodrimenoyl anilides and 4′-methyl-homodrimenthioyl anilides were synthesized and their biological activities were evaluated on five species of fungi (Aspergillus niger, Fusarium solani, Penicillium chrysogenum, P. frequentans, and Alternaria alternata) and two strains of bacteria (Bacillus sp. and Pseudomonas aeruginosa). The synthesis involved the decarboxylative cyclization, condensation and thionation of the said acids, anhydrides or their derivatives with 2-aminothiophenol, 2-aminobenzothiazole, p-toluidine and Lawesson’s reagent. As a result, together with the desired compounds, some unexpected products 8, 25, and 27 were obtained, and the structures and mechanisms for their formation have been proposed. Compounds 4, 9, and 25 showed higher antifungal and antibacterial activity compared to the standards caspofungin (MIC = 1.5 μg/mL) and kanamycin (MIC = 3.0 μg/mL), while compound 8 had comparable activities. In addition, compounds 6, 17, and 27 showed selective antifungal activity at MIC = 2.0, 0.25, and 1.0 μg/mL, respectively. Full article

A series of 25 new benzothiazole–urea–quinoline hybrid compounds were synthesized successfully via a three-step synthetic sequence involving an amidation coupling reaction as a critical step. The structures of the synthesized compounds were confirmed by routine spectroscopic tools (¹H and ¹³C NMR and IR) and by mass spectrometry (HRMS). In vitro evaluation of these hybrid compounds for their antitubercular inhibitory activity against the Mycobacterium tuberculosis H₃₇Rv pMSp12::GPF bioreporter strain was undertaken. Of the 25 tested compounds, 17 exhibited promising anti-TB activities of less than 62.5 µM (MIC₉₀). Specifically, 13 compounds (6b, 6g, 6i–j, 6l, 6o–p, 6r–t, and 6x–y) showed promising activity with MIC₉₀ values in the range of 1–10 µM, while compound 6u, being the most active, exhibited sub-micromolar activity (0.968 µM) in the CAS assay. In addition, minimal cytotoxicity against the HepG2 cell line (cell viability above 75%) in 11 of the 17 compounds, at their respective MIC₉₀ concentrations, was observed, with 6u exhibiting 100% cell viability. The hybridization of the quinoline, urea, and benzothiazole scaffolds demonstrated a synergistic relationship because the activities of resultant hybrids were vastly improved compared to the individual entities. In silico ADME predictions showed that the majority of these compounds have drug-like properties and are less likely to potentially cause cardiotoxicity (QPlogHERG > −5). The results obtained in this study indicate that the majority of the synthesized compounds could serve as valuable starting points for future optimizations as new antimycobacterial agents. Full article

Background: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. Methods: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF₃-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. Results: All compounds showed antibacterial activity with MIC in range of 0.12–0.75 mg/mL and MBC at 0.25–>1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. Conclusion: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF₃ substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds. Full article

Triclocarban (TCC) is a polychlorinated, aromatic, antimicrobial agent commercially used since the 1950s in personal care products for the prevention of spoilage and infections. Humans are frequently exposed to TCC due to its widespread use, leading to its substantial release into the aquatic environment. With the recent ban of TCC from some personal care products, implemented in 2016, many replacement antimicrobial compounds have been studied by researchers. Herein, we report the synthesis and biological activity of a series of diarylureas, analogues of TCC that bear the benzothiazole nucleus as one of the two aryl moieties. Among the studied compounds, 2bF and 2eC showed the highest antimicrobial activity against Staphylococcus aureus, being also more active than TCC, with MIC values of 8 µg/mL versus 16 µg/mL of TCC. Moreover, compound 2bB was much more active than TCC against Enterococcus faecalis, a Gram-positive bacterium that is, unfortunately, strongly responsible for nosocomial infections. Finally, interesting results were found for compound 2bG that, even though less active than the others, exerts an interesting bactericidal action. Full article

The burden of antibiotic resistance necessitates a continued search for new antimicrobials. We evaluated the antimicrobial activities of novel benzothiazoles synthesized by our group. Antibacterial activity was evaluated in vitro in Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, while the antifungal activity was tested in Candida albicans and Aspergillus niger, and expressed as the minimum inhibitory concentration (MIC; µg/mL). MIC values of benzothiazole compounds ranged from 25 to 200 µg/mL. Compounds 3 and 4 gave high antibacterial and moderate antifungal activities, while 10 and 12 showed moderate activity against all tested organisms. In addition, some benzothiazole compounds significantly suppressed the activity of Escherichia coli dihydroorotase and inhibited the dimorphic transition of Candida albicans. Moreover, the active benzothiazole compounds induced DNA and protein leakage in Aspergillus niger spores. Molecular interactions of benzothiazole derivatives with dihydroorotase revealed the formation of hydrogen bonds with the active site residues LEU222 or ASN44. Strong hydrophobic interactions of the bulky thiazole and naphthalene rings at the entrance to the active site might interfere with the access of substrates to their binding sites, which results in dihydroorotase inhibition. Thus, inhibition of dihydroorotase might contribute to the observed antimicrobial actions of these compounds. Full article

The purpose of this study was to investigate the chemical composition and biological activity of the volatile oils (VOs) from the flowers of three buckwheat species, Fagopyrum esculentum, Fagopyrum tataricum and Fagopyrum cymosum. The VOs were obtained from the fresh buckwheat flowers by hydrodistillation, and were analyzed for their chemical composition by gas chromatography-mass spectrometry (GC-MS). Nonanoic acid (7.58%), (E)-3-hexen-1-ol (6.52%), and benzothiazole (5.08%) were the major constituents among the 28 identified components which accounted for 92.89% of the total oil of F. esculentum. 2-Pentadecanone (18.61%), eugenol (17.18%), 1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester (13.19%), and (E,E)-farnesylacetone (7.15%) were the major compounds among the 14 identified components which accounted for 88.48% of the total oil of F. tataricum. Eugenol (12.22%), (E)-3-hexen-1-yl acetate (8.03%), linalool oxide (7.47%), 1-hexanol (7.07%), and benzothiazole (6.72%) were the main compounds of the 20 identified components which accounted for 90.23% of the total oil of F. cymosum. The three VOs were screened to have broad spectrum antibacterial activity with minimum inhibitory concentration (MIC) values ranged from 100.0 μg/mL to 800.0 μg/mL against the tested bacteria, and their median inhibitory concentration (IC₅₀) values were from 68.32 μg/mL to 452.32 μg/mL. Xanthomonas vesicatoria was the most sensitive bacterium. Moreover, the flower VOs of F. esculentum, F. tataricum and F. cymosum also exhibited noteworthy antioxidant capacity with the IC₅₀ value of 354.15 μg/mL, 210.63 μg/mL, and 264.92 μg/mL for the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay, and the value of 242.06 μg/mL, 184.13 μg/mL, and 206.11 μg/mL respectively for the β-carotene-linoleic bleaching test. These results suggested the volatile oils of buckwheat flowers could be potential resource of natural antimicrobial and antioxidant agents. Full article