Twelve novel chalcone derivatives were prepared using the Claisen–Schmidt condensation reaction. The reaction of 4‐acetyl‐5‐furan/thiophene‐pyrazole derivatives 5 with the corresponding aldehydes 6 afforded the targeted chalcone derivatives 7a–l in good yields. The newly synthesized chalcones were fully characterized by spectrometric and elemental analyses. The in vitro anticancer activities of the novel compounds 7a–l were evaluated against four human cancer cell lines: HepG2 (human hepatocellular carcinoma), MCF7 (human Caucasian breast adenocarcinoma), A549 (lung carcinoma), and BJ1 (normal skin fibroblasts). Compound 7g emerged as the most promising compound, with IC50 = 27.7 µg/ml against A549 cells compared to the reference drug doxorubicin (IC50 = 28.3 µg/ml), and IC50 = 26.6 µg/ml against HepG2 cells compared to the reference drug doxorubicin (IC50 = 21.6 µg/ml). The gene expression and DNA damage values and the DNA fragmentation percentages for compound 7g were determined on the lung and liver cell lines. The expression levels of the AMY2A and FOXG1 genes increased significantly (p < 0.01) in the negative samples of lung cancer cells compared with treated cells. Also, the expression values of the PKM and PSPH genes improved significantly (p < 0.01) in the negative samples compared with treated samples of liver cancer cells. The DNA damage values increased significantly (p < 0.01) in treated lung cell line samples (7g) and the positive control. The results showed a significant decrease (p < 0.05) in DNA damage values in the negative samples of liver cancer cells compared to those treated with 7g. However, the DNA fragmentation values increased significantly (p < 0.01) in the treated lung and liver cell line samples compared with the negative control.

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A series of 1,3,4-thiadiazole derivatives were designed and synthesized using N-(4-nitrophenyl)acetohydrazonoyl bromide and 1-[3,5-dimethyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]ethan-1-one as starting materials. The treatment of 1-[3,5-dimethyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]ethan-1-one with methyl hydrazinecarbodithioate or hydrazinecarbothioamide afforded 2-[1-[5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]ethylidene]hydrazine derivatives. The targeted 1,3,4-thiadiazolyl derivatives were prepared by the reaction of 2-[1-[5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl]ethylidene]hydrazine derivatives with hydrazonoyl chloride derivatives. The reaction of N-(4-nitrophenyl)acetohydrazonoyl bromide with 2-[(methylthio)carbonthioyl]hydrazones in absolute ethanol in the presence of triethylamine afforded the corresponding 1,3,4-thiadiazole derivatives. The newly synthesized compounds were fully characterized by 1H NMR, 13C NMR, IR, MS, and elemental analysis. Moreover, the antimicrobial activity of the synthesized 1,3,4-thiadiazole derivatives were tested against E. coli, B. mycoides, and C. albicans. Four compounds outperformed the other produced compounds in terms of antimicrobial activity. Graphical abstract

triazolo[3,4-a]isoquinolin-3-yl)ethan-1-ones 4 were prepared via reaction of C-acetylmethanohydrazonoyl chlorides 1A,B with 6,7-dimethoxy-3,4dihydroisoquinoline 3. Treatment of the latter products 4 with 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehyde derivatives 5 in ethanol in the presence of sodium hydroxide solution at room temperature afforded chalcones 6.Cytotoxic assay was performed for in vitro antitumor screening against caucasian breast adenocarcinoma (MCF7) and hepatocellular carcinoma (HepG2) cell lines.Chalcones 6Ab and 6Ba have promising cytotoxic effects against MCF7 with IC50 values 8.0 and 7.5 µg/mL, respectively. Molecular docking using Mcule.com was carried out, for the most potent compounds 6Ab and 6Ba, against two protiens which are EGFR and DHFR.

Seventeen new furan‐substituted thiadiazolyl hydrazone derivatives bearing 4‐nitrophenyl moiety were designed, synthesized and tested for their in vitro antimicrobial activity. Reaction of N‐(4‐nitrophenyl)‐C‐(furan‐2‐yl)methanohydrazonoyl chloride 1 with 2‐((methylthio)carbonthioyl)hydrazine derivatives 3, 7, 8 and 11–13 in absolute ethanol in the presence of triethylamine at room temperature afforded the corresponding 1,3,4‐thiadiazole derivatives 6, 9, 10 and 14–16. Refluxing of 1‐(3‐(furan‐2‐yl)‐5‐methyl‐1‐(4‐nitrophenyl)‐1H‐pyrazol‐4‐yl)ethan‐1‐one 17 with methyl hydrazinecarbodithioate 18 in absolute ethanol in the presence of few drops of hydrochloric acid yielded methyl‐2‐(1‐(3‐(furan‐2‐yl)‐5‐methyl‐1‐(4‐nitrophenyl)‐1H‐pyrazol‐4‐yl)ethylidene)hydrazine‐1‐carbodithioate 19. The compound 19 was reacted with hydrazonoyl halides 20a‐e in absolute ethanol in the presence of triethylamine afforded the corresponding 1,3,4‐thiadiazoles 24a‐e. The specified compounds were tested for antimicrobial activity against selected model microorganisms. Antimicrobial studies revealed that compounds 6c, 6d and 15 against E. coli, compounds 6b, 6c, 10, 14, 15, 24b and 24c against B. mycoides, and compounds 14, 16, 19 and 24d against C. albicans outperformed other developed compounds in terms of antimicrobial activity.