Computational and in vitro binding studies of theophylline against phosphodiesterases functioning in sperm in presence and absence of pentoxifylline.
Biophys Chem
; 313: 107294, 2024 Oct.
Article
en En
| MEDLINE
| ID: mdl-39029164
ABSTRACT
Fertility is a result of a synergy among the sperm's various functions including capacitation, motility, chemotaxis, acrosome reaction, and, finally, the fertilization of the oocyte. Subpar motility is the most common cause of infertility in males. Cyclic adenosine monophosphate (cAMP) signalling underlies motility and is depleted by the phosphodiesterases (PDEs) in sperm, such as PDE10A, PDE1, and PDE4. Therefore, the PDE inhibitor (PDEI) category of fertility drugs aim to enhance motility in assisted reproduction technologies (ARTs) through inhibition of PDEs, though they might have adverse effects on other physiological variables. For example, the popular drug pentoxifylline (PTX), widely used in ARTs, improves motility but causes premature acrosome reaction and exerts toxicity on the fertilized oocyte. Another xanthine-derived drug, theophylline (TP), has been repurposed for treating infertility, but its mechanism of PDE inhibition remains unexplored. Here, using biophysical and computational approaches, we identified that TP binds to the same binding pocket as PTX with higher affinity than PTX. We also found that PTX and TP co-bind to the same binding pocket, but at different sites.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pentoxifilina
/
Inhibidores de Fosfodiesterasa
/
Espermatozoides
/
Teofilina
/
Hidrolasas Diéster Fosfóricas
Límite:
Humans
/
Male
Idioma:
En
Revista:
Biophys Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Países Bajos