Synthesis of Sildenafil Analogues from Anacardic Acid and Their Phosphodiesterase-5 Inhibition

• Published in: Journal of agricultural and food chemistry 2002-12, Vol.50 (26), p.7709-7713
• Main Authors: Paramashivappa, R, Phani Kumar, P, Subba Rao, P. V, Srinivasa Rao, A
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-GMP Phosphodiesterases; Anacardic Acids; Biological and medical sciences; Chemistry; Cyclic Nucleotide Phosphodiesterases, Type 5; Exact sciences and technology; Genital system. Reproduction; Heterocyclic compounds; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medical sciences; Organic chemistry; Pharmacology. Drug treatments; Phosphodiesterase Inhibitors - chemical synthesis; Phosphodiesterase Inhibitors - pharmacology; Phosphoric Diester Hydrolases - metabolism; Piperazines - chemistry; Piperazines - pharmacology; Preparations and properties; Purines; Salicylates - chemistry; Sildenafil Citrate; Structure-Activity Relationship; Sulfones
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf0258050

Anacardic acid (6-pentadecylsalicylic acid), a major component of cashew nut shell liquid, consists of a heterogeneous mixture of monoenes, dienes, and trienes. The enes mixture of anacardic acid was hydrogenated to a saturated compound. Using saturated anacardic acid as a starting material, analogues of sildenafil [a potent phosphodiesterase-5 (PDE5) inhibitor and an orally active drug for the treatment of erectile dysfunction] were synthesized, to observe the effect of the pentadecyl side chain on PDE5 inhibition. The synthesized compounds were characterized by spectral studies and tested for PDE5 inhibition, and the results were compared with those obtained with sildenafil. Keywords: Anacardic acid; cashew nut shell liquid; sildenafil; PDE5 inhibitor; erectile dysfunction