Anti-parkinsonian, anti-inflammatory, anti-microbial, analgesic, anti-hyperglycemic and anticancer activities of poly-fused ring pyrimidine derivatives.

Purpose: To investigate the anti-inflammatory, anti-cancer, anti-parkinsonian, anti-microbial, analgesic, and anti-hyperglycemic properties of a variety of poly-fused pyrimidine derivatives. Methods: A novel series of fused pyrimidine derivatives 1-6 were synthesized by reacting amino pyrazole derivatives with active methylene derivatives to give the corresponding compounds 1-6. Anti-parkinsonian activity was investigated with benzotropene as a reference drug, anti-inflammatory effect in mice was evaluated using carrageenan in paw edema with indomethacin as reference drug, antimicrobial activity was assessed using nutritional agar with ciprofloxacin and ketoconazole as reference drugs, analgesic activity was evaluated using valdecoxib as reference drug, anti-hyperglycemic activity was investigated using alloxan and sucrose models (SLM) with pioglitazone as reference drug and anticancer activity was investigated using the MTT micro-cultured tetrazolium assay method with doxorubicin as reference drug. Results: Pyrimidine derivatives 1-6 possess significant active anti-parkinsonian, anti-inflammatory, antimicrobial, analgesic, anti-hyperglycemic and anticancer activities in comparison to the reference drugs used for each model. Compared to Benzotropene®, compounds 1 and 3 showed a significantly stronger anti-parkinsonian activity (p < 0.03). Compound 3 showed a significantly stronger anti-inflammatory effect than Indomethacin® (p < 0.05). Compounds 5 and 6 exhibited significant anti-microbial activity compared to ciprofloxacin® (p < 0.05). Compounds 4 and 6 exhibited significantly improved analgesic activity as compared to Valdecoxib® (p < 0.01). Compounds 1 and 3 exhibited significantly higher antihyperglycemic effects in SLM model when compared to pioglitazone® (p < 0.02). Compound 5 demonstrated the highest activity against human colon cancer cell line (HT-29) and human prostate cancer cell line (DU145), and also, significantly improved level of efficacy against human lung cancer cell line (A549) compared to Doxorubicin® (p < 0.02). Conclusion: Using the six pyrimidine derivatives 1 - 6 as a lead molecule, a novel class of clinically beneficial anti-cancer, anti-inflammatory, anti-microbial, analgesic, and anti-hyperglycemic drugs may be produced. [ABSTRACT FROM AUTHOR]