Schiff bases of chitosan (CS) were prepared by reaction of four different heterocyclic compounds, namely, 1,3-dimethyl-2,4,6-trioxohexahydropyrimidine-5-carbaldehyde (M1), 3-acetyl-2H-chromen-2-one (M2), 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (M3), and 4-oxo-4H-chromene-3-carbaldehyde (M4), with CS using thermal and ultrasound approaches. CS Schiff base formation was confirmed by using FT-IR, XRD, and TGA. Characteristic data show that amino groups in chitosan reacted with the functional group in the heterocyclic compound to form the Schiff base. CS Schiff bases show thermal stability more than pure CS. The antimicrobial activity of Schiff bases was tested against +ve Gram bacteria and -ve Gram bacteria. The result shows that Schiff bases prepared by temperature and ultrasound methods possess high antimicrobial activity against +ve Gram bacteria and -ve Gram bacteria; in comparison, Schiff bases produced by the ultrasound method have higher antimicrobial activity. The Schiff base (CSM4U), prepared by the ultrasound method by reaction of CS with 4-oxo-4H-chromene-3-carbaldehyde, exhibited higher antimicrobial activity than Gentamicin as an antibacterial agent. The inhibition range caused by CSM4U was between 19 and 27 mm. Moreover, CSM4U also acted as an antifungal agent, causing an inhibition zone of 21 mm for both Candida albicans and Candida tropicalis, which was higher than that of Terbinafine.

A series of new spiro-heterocycles engrafted spirooxindole/pyrrolidine/thiochromene scaffolds was synthesized by the three-component 1,3-dipolar cycloaddition reactions in a fully controlled regio- and stereo-selective fashion. Condensation of several substituted isatin derivatives with L-proline generated the azomethine ylides which subsequently reacted with chalcones based thiochromene scaffold, and finally afforded the target spiro-compounds. This simple protocol furnished a structurally complex, biologically relevant spiro-heterocycles in good yields through a one-pot process. All synthesized chalcone-based thiochromene, along with the spirooxindole/pyrrolidine/thiochromene scaffolds, were tested for their anticancer activity against four cancer cell lines (PC3, HeLa, MCF-7, and MDA-MB231). Toxicity of these compounds was also evaluated against human fibroblast BJ cell line, and they appeared to be not cytotoxic. For the prostate cancer (PC3) cell line, the most active hybrid, among synthesized series, was compound (7f, IC₅₀ = 8.7 ± 0.7 µM). The most potent spirooxindole/pyrrolidine/thiochromene hybrid against cervical (HeLa) cancer cells was compound (7k, IC₅₀ = 8.4 ± 0.5 µM) having chlorine and p-trifluoromethyl substituents attached to phenyl rings. Finally, against the MCF-7 and MDA-MB231 breast cancer cell lines, compound (7d) was the most active member of this series (IC₅₀ = 7.36 ± 0.37, and 9.44 ± 0.32 µM, respectively).

Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt2). The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques (1H-NMR, 13C-NMR, IR, MS, and CHN). The synthesized compounds were evaluated for their antibacterial and antifungal activities against S. aureus ATCC 29213, E. faecalis ATCC29212, B. subtilis ATCC 10400, and C. albicans ATCC 2091 using agar Cup plate method. Compound 4b exhibited the best activity against B. subtilis and E. faecalis with MIC = 16 µg/L. Compounds 4e and 4l exhibited the best activity against S. aureus with MIC = 16 µg/L. Compound 4k exhibited the best activity against B. subtilis with MIC = 8 µg/L. Compounds 4o was the most active compounds against C. albicans with MIC = 4 µg/L. In-silico predictions were utilized to investigate the structure activity relationship of all the newly synthesized antimicrobial compounds. In this regard, a ligand-based pharmacophore model was developed highlighting the key features required for general antimicrobial activity. While the molecular docking was carried out to predict the most probable inhibition and binding mechanisms of these antibacterial and antifungal agents using the MOE docking suite against few reported target proteins.

A new series of thiobarbituric (thiopyrimidine trione) enamine derivatives and its analogues barbituric acid derivatives was synthesised, characterised, and screen for in vitro evaluation of α-glucosidase enzyme inhibition and anti-glycation activity. This series of compounds were found to inhibit α-glucosidase activity in a reversible mixed-type manner with IC₅₀ between 264.07 ± 1.87 and 448.63 ± 2.46 µM. Molecular docking studies indicated that compounds of 3g, 3i, 3j, and 5 are located close to the active site of α-glucosidase, which may cover the active pocket, thereby inhibiting the binding of the substrate to the enzyme. Thiopyrimidine trione derivatives also inhibited the generation of advanced glycation end-products (AGEs), which cause long-term complications in diabetes. While, compounds 3a–k, 5, and 6 showed significant to moderate anti-glycation activity (IC₅₀ = 31.5 ± 0.81 to 554.76 ± 9.1 µM).

A new series of di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were synthesized. Initially, azomethine ylides were generated via reaction of the substituted isatins 3a–f (isatin, 3a, 6-chloroisatin, 3b, 5-fluoroisatin, 3c, 5-nitroisatin, 3d, 5-methoxyisatin, 3e, and 5-methylisatin, 3f, and (2S)-octahydro-1H-indole-2-carboxylic acid 2, in situ azomethine ylides reacted with the cyclohexanone based-chalcone 1a–f to afford the target di-spirooxindole compounds 4a–n. This one-pot method provided diverse structurally complex molecules, with biologically relevant spirocycles in a good yields. All synthesized di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were evaluated for their anticancer activity against four cancer cell lines, including prostate PC3, cervical HeLa, and breast (MCF-7, and MDA-MB231) cancer cell lines. The cytotoxicity of these di-spirooxindole analogs was also examined against human fibroblast BJ cell lines, and they appeared to be non-cytotoxic. Compound 4b was identified as the most active member of this series against prostate cancer cell line PC3 (IC₅₀ = 3.7 ± 1.0 µM). The cyclohexanone engrafted di-spirooxindole analogs 4a and 4l (IC₅₀ = 7.1 ± 0.2, and 7.2 ± 0.5 µM, respectively) were active against HeLa cancer cells, whereas NO₂ substituted isatin ring and meta-fluoro-substituted (2E,6E)-2,6-dibenzylidenecyclohexanone containing 4i (IC₅₀ = 7.63 ± 0.08 µM) appeared to be a promising agent against the triple negative breast cancer MDA-MB231 cell line. To explore the plausible mechanism of anticancer activity of di-spirooxindole analogs, molecular docking studies were investigated which suggested that spirooxindole analogs potentially inhibit the activity of MDM2.