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.