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.

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.

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Phthalazines have received considerable attention for their wide antimicrobial activity. Regiospecific nucleophilic attack of 4‐benzylphthalazin‐1‐ol by the 1‐oxo rather than the aza group on different alkyl halides gave novel phthalazine heterocyclic derivatives. Moreover, a variety of nucleosides bonded to electron‐withdrawing groups were synthesized using 4‐benzylphthalazine‐1‐ol. The density functional theory has been used to investigate the electronic structure of the synthesized compounds. All of the synthesized derivatives showed remarkable activity when tested against Gram‐positive and Gram‐negative bacteria, Aspergillus niger, and Candida albicans. The reactivity of these nucleosides was expected to arise from their bonding with the lone pair of N‐atom of the macromolecules of bacteria. These bonding were expected to inhibit the enzyme by forming highly stable complex with lower highest occupied molecular orbital energy. The structures of these synthesized derivatives were established by Fourier transform infrared, 1H‐NMR, and 13C‐NMR spectroscopic evidence.

Because of the remarkable pharmacodynamics and chemotherapeutics activities of thiadiazolopyrimidines, a new series of 1,3,4‐thiadiazolo[3,2‐a] pyrimidine derivatives have been synthesized by reacting 5‐substituted‐2‐aminothiadiazoles 1a,b with different reagents: active methylenic compounds, benzaldehyde under different conditions, isatin, and cyclic ketones. The structures of the novel compounds have been inferred by spectroscopic methods (infrared, 1H‐NMR, 13C‐NMR, and mass spectrometry) and elemental analyses. The newly synthesized compounds were screened against four bacterial strains (Staphylococcus aureus and Listeria monocytogenes as Gram positive and Pseudomonas aeruginosa and Salmonella typhimurium as Gram negative) and two fungi (Aspergillus niger and Candida albicans) using agar diffusion assay. Most of the compounds showed activity against the tested microorganisms with different extents. The in vitro anticancer activities of these compounds were assessed against four human tumor cell lines; they were found to exhibit different cytotoxic effects. Such results mean that these derivatives can be further utilized as promising anticancer agents.