The current study was directed toward developing a new series of fused heterocycles incorporating indazolylthiazole moiety. The newly synthesized compounds were characterized through elemental analysis and spectral data (IR, 1H-NMR, 13C-NMR, and Mass Spectrometry). The cytotoxic effect of the newly synthesized compounds was evaluated against normal human cells (HFB-4) and cancer cell lines (HepG-2 and Caco-2). Among the synthesized compounds, derivatives 4, and 6 revealed a significant selective antitumor activity, in a dose-dependent manner, against both HepG-2 and Caco-2 cell lines, with lower risk toward HFB-4 cells (normal cells). Derivative 8 revealed the maximum antitumor activity toward both tumor cell lines, with an SI value of about 26 and IC50 value of about 5.9 μg/mL. The effect of these derivatives (8, 4, and 6) upon the expression of 5 tumor regulating genes was studied through quantitative real-time PCR, where its interaction with these genes was simulated through the molecular docking study. Furthermore, the antimicrobial activity results revealed that compounds 2, 7, 8, and 9 have a potential antimicrobial activity, with maximum broad-spectrum activity through compound 3 against the three tested pathogens: Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans. The newly prepared compounds also revealed anti-biofilm formation activity with maximum activity against Streptococcus mutans, Pseudomonas aeruginosa, and Candida albicans, respectively.

The present work illustrates the treatment of 5-amino-1,3-diphenyl-1H-pyrazole-4-carbonitrile (1) with maleic, phthalic anhydrides, acetyl chloride, and benzene sulfonyl chloride to afford the pyrazole derivatives 2-5. The treatment of pyrazole derivative 1 with some active methylene reagents namely: malononitrile, cyanoacetamide, ethyl acetoacetate afforded the pyrazolopyridine 6-9. Reaction of compound 1 with acetic anhydride gave the pyrazolopyrimidinone 10, which was allowed to react with P2S5 and POCl3 to give the thione 11 and the chloro 12 derivatives. The reaction of compounds 11 and 12 with thiosemicarbazide under different conditions gave 13 and 14. Compound 12 when reacted with hydrazine hydrate and p-toluidine gave compounds 15 and 16. The reaction of compound 10 with ethyl chloroacetate gave compound 17 which was allowed to react with thiosemicarbazide to give 22 and also to consecutive reactions with hydrazine hydrate, carbon disulfide, piperidine, hydrazine hydrate to give compounds 18-21. Finally, compound 1 was reacted with chloroacetic acid, hydrated hydrazine, urea, thiourea, benzaldehyde and triethylamine to give compounds 23-29. The newly prepared compounds were characterized by using IR, 13 C-NMR, 1 H-NMR, and mass spectral data. Some new pyrazole derivatives showed highly antibacterial activities.

A Biginelli one-pot three-component reaction involving cyclohexanone, aromatic/or heterocyclic aldehyde, and urea thiourea or guanidine HCl was applied in this work to prepare quinazolin-2(1H)one derivatives under solvent free and microwave irradiation assistance as well as conventional method. The major advantages of this protocol are high yields, operational simplicity, short reaction time and environment friendly. The purity of the synthesized compounds was characterized by means of IR, 1 H NMR, 13 C NMR, mass spectral and elemental analysis.

A new series of pyrazoles have been synthesized via 2-(3-phenyl-1, 3, 4, 5, 6, 7-hexahydro-2H-indazol-2-yl)thiazol-4(5H)-one(2), which on treatment with phosphorus pentachloride and phosphoryl chloride afforded 4-chlorothiazole derivative(3). Reaction of 3 with hydrazine hydrate in boiling gave 4-hydrazineylthiazole derivative (4). Heterocyclization of 4 with aromatic aldehydes and active methylene compounds afforded the pyrazole derivatives (5-8).The synthesized pyrazoles (5-8) and their precursor (1-4) were evaluated for antimicrobial activities. All prepared compounds revealed abroad-spectrum antimicrobial activity with maximum inhibition activity against Streptococcus mutans. Compound 3 revealed the most potent antibiofilm inhibition activity against the three used pathogens. Additionally, all compounds (1-8) were also tested for cytotoxic activity against hepatoma, and colon carcinoma cell lines. Compounds 3, 5 and 7 displayed good to excellent activity against all tested tumor cells with IC50 values ranged from 6.13 to 23.85 μg/ml. On the other hand, all compounds were evaluated for cytotoxic activity on normal human melanocytes cell lines and found to be signified its high selectivity toward cancer cells than normal cells. Moreover, the molecular modeling study was carried out using (MOE 2014) software. The computational studies are confirming the results in biological activity.

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