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

Abstract

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, anti-microbial 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, anti-microbial, 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 anti-hyperglycemic 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.