A new series of 5-(3,5-dinitrophenyl)-1,3,4-thiadiazole derivatives were prepared and evaluated for their in vitro antimicrobial, antitumor, and DHFR inhibition activity. Compounds 9, 10, 13, and 16 showed strong and broad-spectrum antimicrobial activity comparable to Amoxicillin and Fluconazole as positive antibiotic and antifungal controls, respectively. Compounds 6, 14, and 15 exhibited antitumor activity against four human cancer cell lines, CCRF-CEM leukemia, HCT-15 colon, PC-3 prostate, and UACC-257 melanoma cell lines using Doxorubicin as a reference drug. Compounds 10, 13, 14, and 15 proved to be the most active DHFR inhibitors with an IC50 range of 0.04 ± 0.82–1.00 ± 0.85 µM, in comparison with Methotrexate (IC50 = 0.14 ± 1.38 µM). The highly potent DHFR inhibitors shared a similar molecular docking mode and made a critical hydrogen bond and arene‒arene interactions via Ser59 and Phe31 amino acid residues, respectively.

A new series of heterocycles was synthesized via the reaction of readily obtainable 1,3‐diphenylpyrazole‐4‐carboxaldehyde thiosemicarbazone with many carbon electrophiles, for example, chloroacetic acid, chloroacetyl chloride, ethyl chloroacetate, dimethyl acetylenedicarboxylate, maleic anhydride, 3′‐nitro‐ω‐bromoacetophenone, malonic acid, acetylacetone, ethyl benzoylacetate, arylidene malononitrile, and ethyl cyanoacetate in attempt to construct imidazolidinone, thiazolidinone, thiazole, and pyrimidine derivatives. The behavior of the titled compound towards hydrazine hydrate was investigated, in addition to the ring closure under different conditions. Also, the reactions with 2‐chloroquinoline‐3‐carboxaldehyde and chromone‐3‐carboxaldehyde were discussed. The structures of all products obtained were substantiated from their analytical and spectral data. The antitumor and antimicrobial activities of the synthesized compounds were examined.

Spiro‐oxo‐indole/pyrrolidine‐thiophene base possessed significant pharmacological activity. The [3 + 2] cycloaddition reactions of thia‐methine ylide respected through multi‐component reaction affording regioselective and stereoselective spiroindoline‐3,2′‐tetrahydrothiophene derivative 3. Reaction of such compound with different electrophilic and nucleophilic reagents afforded bioactive heterocyclic compounds 4–16. Biological evaluation showed that these synthesized spiro‐pyrrolidine exhibited moderate to good cytotoxic activity. Among them, compounds 7 and 14 displayed the best cytotoxic activity against MCF‐7 and Wl‐38 cells with the IC50 values of 7.02 ± 0.6 and 8.97 ± 0.9 μm (very strong), respectively. Compounds 4, 5, and 12 exhibited strong cytotoxicity's with IC50 16.28 ± 1.7, 11.16 ± 1.1, and 19.14 ± 1.7 μm, respectively, against MCF‐7 mammary gland cell line. All compound structures were supported by spectroscopic data and elemental analysis.

A pyrimidinethione derivative namely, 6-(1,3-diphenyl-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile, was readily synthesized and reacted with carbon electrophiles in an attempt to synthesize selected fused heterocycles. The reactivity of 6-(1,3-diphenyl-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile was investigated towards selected nitrogen nucleophiles. Thiation and hydrolysis reactions of the tetrahydropyrimidine derivative were investigated. Antitumor and antimicrobial activity evaluation of some of the synthesized products exhibited promising results.

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