Two series of novel 2-[[1-(5-methyl-1-phenyl-5-substituted-1H-pyrazol-4-yl)ethylidene]hydrazono]-3-phenyl-2,3-dihydro-1,3,4-thiadiazole derivatives and 2-[5-(4-chlorophenyl)-5′-methyl-1′-phenyl-3,4-dihydro-1′H,2H-[3,4′-bipyrazol]-2-yl]-4-substituted-5-(phenyldiazenyl)thiazole derivatives were prepared from reaction of hydrazonoyl halides with methyl 2-[1-(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethylidene]hydrazine-carbodithioate and thiosemicarbazide derivative, respectively. The newly synthesized derivatives were elucidated by elemental analysis, spectral data, and alternative synthetic routes, whenever possible. The anti-cancer activity of the selected products against the breast carcinoma cell line MCF-7 was determined by WST-1 assay indicating concentration-dependent cellular growth inhibitory effect especially for three compounds with dose response curves indicating IC
 50 values of 21.3 ± 0.72, 21.3 ± 0.72, and 23.56 ± 0.81 µg cm−3, respectively. Confocal laser scanning imaging of the treated cells stained by rhodamin 123 and acridine orange dyes confirms that the selected compounds inhibit the mitochondrial lactate dehydrogenase enzymes. The obtained results revealed promising anticancer activity.

Synthesis, characterization, and pharmacological evaluation of some novel thiadiazoles and thiazoles incorporating pyrazole moiety as anticancer agents

Synthesis and Anti‐cancer Activity of 1,3,4‐Thiadiazole and 1,3‐Thiazole Derivatives Having 1,3,4‐Oxadiazole Moiety

Reactions of hydrazonoyl halides and each of methyl 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbodithioate and 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazine-1-carbothioamide afforded 2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazono)-3-phenyl-5-substituted-2,3-dihydro-1,3,4-thiadiazoles and 5-(4-substituted)diazenyl)-2-(2-(1-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)ethylidene)hydrazinyl)-4-arylthiazoles, respectively. Analogously, the reactions of hydrazonoyl halides with 7-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-5-phenyl-2-thioxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-one gave 3-(4-substituted)-8-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-6-phenyl-1-arylpyrido[2,3-d]-[1,2,4]-triazolo-[4,3-a]pyrimidin- 5(1H)-ones in a good yield. The structures of the newly synthesized were elucidated via elemental analysis, spectral data and alternative synthesis routes whenever possible. Twelve of the newly synthesized compounds have been evaluated for their antitumor activity against human breast carcinoma (MCF-7) and human hepatocellular carcinoma (HepG2) cell lines. Their structure activity relationships (SAR) were also studied. The 1,3,4-thiadiazole derivative 9b (IC50 = 2.94 µM) has promising antitumor activity against the human hepatocellular carcinoma cell line and the thiazole derivative 12a has promising inhibitory activity against both the human hepatocellular carcinoma cell line and the breast carcinoma cell line (IC50 = 1.19, and 3.4 µM, respectively).

https://www.mdpi.com/1420-3049/20/1/1357/pdf

Synthesis and cytotoxicity evaluation of some novel thiazoles, thiadiazoles, and pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5(1H)-ones incorporating triazole moiety.

2-(3-(1H-Indol-3-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-substituted-5-(substituted diazenyl)thiazoles and 2-(1H-indol-3-yl)-9-substituted-4,7-disubstituted pyrido[3,2-e][1,2,4]triazolo[4,3-a]pyrimidin-5(7H)-ones were synthesized via reaction of hydrazonoyl halides with each of 3-(1H-indol-2-yl)-5-(p-tolyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide and 7-(1H-indol-3-yl)-2- thioxo-5-substituted-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ones, respectively. Also, hydrazonoyl halides were reacted with N’-(1-(1H-indol-3-yl)ethylidene)-2-cyanoacetohydrazide to afford 1,3,4-thiadiazole derivatives. Structures of the new synthesis were elucidated on the basis of elemental analysis, spectral data, and alternative synthetic routes whenever possible. Fifteen of the new compounds have been evaluated for their antitumor activity against the MCF-7 human breast carcinoma cell line. The results indicated that many of the tested compounds showed moderate to high anticancer activity when compared with doxorubicin as a reference drug.

https://www.mdpi.com/1420-3049/21/7/929/pdf

Synthesis of New 3-Heteroarylindoles as Potential Anticancer Agents

A novel series of some hydrazones bearing thiazole moiety were generated via solvent-drop grinding of thiazole carbohydrazide 2 with various carbonyl compounds. Also, dehydrative-cyclocondensation of 2 with active methylene compounds or anhydrides gave the respective pyarzole or pyrazine derivatives. The structures of the newly synthesized compounds were established based on spectroscopic evidences and their alternative syntheses. Additionally, the anti-viral activity of all the products was tested against SARS-CoV-2 main protease (Mpro) using molecular docking combined with molecular dynamics simulation (MDS). The average binding affinities of the compounds 3a, 3b, and 3c (-8.1 ± 0.33 kcal/mol, -8.0 ± 0.35 kcal/mol, and -8.2 ± 0.21 kcal/mol, respectively) are better than that of the positive control Nelfinavir (-6.9 ± 0.51 kcal/mol). This shows the possibility of these three compounds to effectively bind to SARS-CoV-2 Mpro and hence, contradict the virus lifecycle.

https://www.mdpi.com/1420-3049/25/19/4565/pdf

Clean Grinding Technique: A Facile Synthesis and In Silico Antiviral Activity of Hydrazones, Pyrazoles, and Pyrazines Bearing Thiazole Moiety against SARS-CoV-2 Main Protease (M(pro))

A Facile Green Synthesis and Anti-Cancer Activity of bis-Arylhydrazononitriles, Triazolo[5,1-c][1,2,4]triazine, and 1,3,4-Thiadiazolines

Synthesis and reactions of 3-thioxo[1,2,4]-triazino[3,2-b]quinazolin-10-ones

Pyrrole derivative (I) is used as starting material for a series of title compounds of type (III), (V), (VII), and (XI).

A Facile Green Synthesis and Anticancer Activity of Bis‐arylhydrazononitriles, Triazolo[5,1‐c][1,2,4]triazine, and 1,3,4‐Thiadiazolines.

Reactions of 3-Amino/Substituted Amino-6-benzyl-5-thioxo- and -5-chloro-1,2,4-triazines: Synthesis of 3,5-Substituted Diamino-1,2,4-triazines and 5-Amino/Substituted Amino-8-benzyl-3-thioxo-s-triazolo(4,3-d)(1,2,4)triazines

Thiation of [1,2,4]triazino[3,2-b]quinazoline-3,10-dione 1 proceeds selectively to give the 3-thioxo-analog 3. The latter was converted to the corresponding 3-methylthio derivative 4 which was reacted with aniline and hydrazine to give the corresponding anilino- and hydrazino derivatives 5 and 7. Compound 7 was converted to the hydrazones 8a,b and into the novel heterocyclic ring systems [1,2,4]triazolo[4′,3′:4,5][1,2,4]triazino-[3,2-b]quinazolin-7-ones 9, 10a,b and tetrazolo[1′,5′:4,5][1,2,4]triazino[3,2-b]quinazolin-7-one 11.

Ali M. El-Zanaty

Papers

A Facile Green Synthesis and Anti-Cancer Activity of bis-Arylhydrazononitriles, Triazolo[5,1-c][1,2,4]triazine, and 1,3,4-Thiadiazolines

Synthesis and reactions of 3-thioxo[1,2,4]-triazino[3,2-b]quinazolin-10-ones

A Facile Green Synthesis and Anticancer Activity of Bis‐arylhydrazononitriles, Triazolo[5,1‐c][1,2,4]triazine, and 1,3,4‐Thiadiazolines.

Reactions of 3-Amino/Substituted Amino-6-benzyl-5-thioxo- and -5-chloro-1,2,4-triazines: Synthesis of 3,5-Substituted Diamino-1,2,4-triazines and 5-Amino/Substituted Amino-8-benzyl-3-thioxo-s-triazolo(4,3-d)(1,2,4)triazines

Synthesis and Reactions of 3-Thioxo(1,2,4)triazino(3,2-b)quinazolin-10-ones.