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The reaction of cyanoacetylhydrazine with chloroacetyl chloride gave N'-(2-chloroacetyl)-2-cyanoacetohydrazide. The latter underwent cyclization to afford 1-(5 amino-3-hydroxy-1H-pyrazol-1-yl)-2-chloroethanone, which underwent nucleophilic substitution to give 3-(5-amino-3-hydroxy-1H-pyrazol-1-yl)-3-oxopropanenitrile. The latter two compounds were used as key synthons to synthesize new thiophene, pyran, thiazole and some fused heterocyclic derivatives. The antitumor activity of the newly synthesized compounds was evaluated against three human tumor cells lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) and some of these compounds were found to exhibit much higher inhibitory effects towards the three tumor cell lines than the Gram positive control doxorubicin.

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The reaction of the 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetonitrile (1) with salicylaldehyde (2) in 1,4-dioxane containing a catalytic amount of piperidine gave the coumarin derivative 3. The latter reacted with different reagents to give pyrano that compounds 7a, 8a, 10b, 13b, 15b, 18a, 19b, 19c, and 19d showed higher activity compared to the rest of the compounds. In addition to this, toxicity of such active compounds was studied against shrimp larvae where compounds 10b, 18a, 19c and 19d showed to be non-toxic against the tested organisms.

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Twenty-four analogues of benzimidazole-based thiazoles (1–24) were synthesized and assessed for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory potential. All analogues were found to exhibit good inhibitory potential against cholinesterase enzymes, having IC50 values in the ranges of 0.10 ± 0.05 to 11.10 ± 0.30µM (for AChE) and 0.20 ± 0.050µM to 14.20 ± 0.10µM (for BuChE) as compared to the standard drug Donepezil (IC50= 2.16 ± 0.12 and 4.5 ± 0.11 µM, respectively). Among the series, analogues 16 and 21 were found to be the most potent inhibitors of AChE and BuChE enzymes. The number (s), types, electron-donating or -withdrawing effects and position of the substituent(s) on the both phenyl rings B & C were the primary determinants of the structure-activity relationship (SAR). In order to understand how the most active derivatives interact with the amino acids in the active site of the enzyme, molecular docking studies were conducted. The results obtained supported the experimental data. Additionally, the structures of all newly synthesized compounds were elucidated by using several spectroscopic methods like 13C-NMR, 1H-NMR and HR EIMS.