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Microbial resistance is a big concern worldwide, making the development of new antimicrobial drugs difficult. The thiazole and pyrazole rings are important heterocyclic compounds utilized to produce a variety of antimicrobial medications. As a result, a series of new bis-thiazolyl-pyrazole derivatives 3, 4a-c, 5a, b, and 6a-c was synthesized by reacting bis hydrazonoyl bromide with several active methylene reagents in a one-pot reaction. The assigned structure was characterized entirely based on elemental and spectral analyses. The antimicrobial activity represented by MIC was performed using a resazurin-based turbidimetric (TB) assay. The results exhibited good antimicrobial activity against gram-positive strains, especially S. aureus (ATCC6538) while showing poor to moderate activity against gram-negative and fungal strains. Furthermore, the most active derivatives 3, 4a, 4c, and 5b were evaluated for MIC, MBC, antibiofilm, hemolytic assay, and drug combination testing against two S. aureus (ATCC6538) and MRSA (ACL18) strains. Additionally, bis-thiazolyl pyrazole 3, 4c, and 5b exhibited more potent inhibitory activity for DHFR with IC50 values (6.34 ± 0.26, 7.49 ± 0.28, and 3.81 ± 0.16 µM), respectively, compared with Trimethoprim (8.34 ± 0.11 µM). The bis-1-(substituted-thiazol-2-yl)-1H-pyrazole-4-carbonitrile derivative 5b was the most active member with MIC values ranging from (0.12–0.25 µM) compared to Vancomycin (1–2 µM), and MBC values ranging from (0.5–1 µM) for S. aureus (ATCC6538) and MRSA (ACL18). Surprisingly, compound 5b displayed bactericidal behavior, synergistic effect with three commercial antibiotics, and inhibited DHFR with 2.1 folds higher than Trimethoprim. Finally, good findings were obtained from in silico investigations incorporating toxicity prediction and molecular docking simulation.

Thienopyrazole compound was used as a key synthon for a one- two- and three- pot component synthesis of new fused heterocyclic moieties which are known to have different biological activities. The investigated compounds were previously synthesized by environmentally benign techniques besides the conventional heating. The current study focused on biological evaluation of cytotoxicity, anti-hemolytic and antioxidant activities of some thienopyrazole compounds. The results showed the strongest anti-hemolytic and antioxidant activities are compounds 3a and 14c, respectively. All compounds were examined against normal human lung fibroblast cell line (WI-38) and four human cancer cell lines as human prostate cancer (PC-3), Hepatocellular carcinoma (HEPG-2), Colorectal carcinoma (HCT-116) and Epitheliod carcinoma (Hela). Molecular docking was performed inside the active site of P53 for compounds 1, 2, 11b and 14c. Moreover, quantum chemical calculations were performed on the selected compounds. Both techniques suggested that compound 1 displays high binding affinity in the P53 active site with respect to compound 2 while compound 14c owns a lower affinity with respect to 11b thereby suggesting that compound 11b may possibly act as P53 inhibitor and thus may participate in anticancer activity.

A series of new magenta azomethine reactive disperse dyes were synthesized and applied into polyester/cotton blend fabrics. Various spectroscopic and analytical techniques characterized all the synthesized dyes. The obtained data and theoretical values of all the synthesized molecules were in good agreement with the proposed molecular structure. These dyes have proven their efficiency in dyeing blend fabrics, as they give satisfactory results in fastness properties, colorimetric data and exhaustion, fixation study. Moreover, the dyed fabrics were tested for ultraviolet protection factor and offered high ultraviolet protection. The advantage of synthesizing these dyes is quite facile, and scale-up is feasible, preferring industrial dyeing applications. The designed thiazole azomethine dyes exhibited broad-spectrum antibacterial agents against MDR Gram-positive and Gram-negative bacterial isolates, which will facilitate their rational usage in multiple therapeutic applications. Our findings also demonstrate the possibility of using gamma radiation for sterilization of dyed fabrics and the ability of radiation to intensify their antibacterial activities, thereby inhibiting any bacterial growth on the surface of textiles. The molecular docking study showed good binding as a preferred mode between the dyes and DNA gyrase's active site (2XCT).

Some new azo dye derivatives having pyrazole and trichlorotriazine moieties were synthesized and were evaluated as reactive dyes for the exhaust dyeing of cotton fiber. The title dyes 5a–c were synthesized from reactions of diazonium salts of 3-substituted-1-phenyl-5-aminopyrazoles 2a–c with 6-amino-7-hydroxy-2-naphthalenesulfonic acid, 4-amino-5-hydroxynaphthalene-2,7-disulfonic acid and/or cyanuric chloride. Other reactive dyes 7a–f were synthesized from reaction of cyanuric chloride and 4-arylazo-3-substituted-1-phenyl-5-aminopyrazoles 6a–f. The synthesized dyes were applied to cotton fiber and their color fastness to light, washing, perspiration, and rubbing were also measured. The dyes showed good to moderate affinity to cotton fiber. The biological screening showed that most of the tested compounds display promising antimicrobial activities against the tested microorganisms.

The chemical behavior of 4-(dimethylaminomethylene)-1-phenyl-3-(pyridin-3-yl)-1 H -pyrazol-5(4 H )-one (enaminone) ( 2 ) toward some active methylene reagents has been reported to give pyrazolopyridine derivatives. All the reactions were carried out by conventional heating and microwave irradiation technique. The antioxidant activity of the prepared compounds was studied using 1,1-phenyl-2-picrylhydrazyl (DPPH) assay. Compounds ( 4c ) and ( 4d ) showed the highest activity. The antitumor activity against liver and breast cell lines was tested. Compounds ( 6 ), ( 9 ) and ( 11 ) showed the highest activity for liver cell line while compounds ( 6 ) and ( 9 ) showed the highest activity for breast cell line. Compounds ( 4a – d ) were screened for their antibacterial activity against Gram-positive, Gram-negative bacteria and antifungal activity.

An efficient one-pot synthesis in multi-component system (MRCs) for the preparation of pyrazolo[3,4- b ]pyridine derivatives from the reaction of 5-amino-1-phenyl-3-(pyridin-3-yl)-1 H -pyrazole with 4-anisaldehyde and p -substituted β-ketonitriles or with pyruvic acid and some aromatic aldehydes in acetic acid medium. The reactions were carried out by two different techniques, conventional heating and microwave irradiation. These compounds were screened for their antibacterial activity against Gram-positive bacteria ( Bacillus ), Gram-negative bacteria ( Escherichia coli, Enterobacter cloaca and serratia ) and antifungal activity against Fusarium Oxysporum and Penicillium expansum . Also, among the synthesized compounds 4a – f tested for antitumor activity against liver cell line. Compounds 6-(4-Fluorophenyl)-4-(4-methoxyphenyl)-1-phenyl-3-(pyridin-3-yl)-1H-pyrazolo[3,4- b ]pyridine-5-carbonitrile ( 4e ) and 4-(4-Methoxyphenyl)-1-phenyl-3,6-di(pyridin-3-yl)-1H-pyrazolo[3,4- b ] pyridine-5-carbonitrile ( 4a ) showed the highest activity.

Diazotized aryl amines were coupled with 3-substituted 5-amino pyrazoles to produce a series of novel 3-substituted 5-amino-4-arylazopyrazoles. Also, 3-substituted 5-amino-pyrazoles were diazotized and coupled with different phenols to give the corresponding novel 3-substituted 5-aryl azo pyrazoles. These dyes were characterized by elemental analysis and spectral data, applied to different types of fibres (wool, polyester and a blend of wool/polyester as disperse dyes) and their fastness properties were evaluated.