Computational, biochemical and ex vivo evaluation of xanthine derivatives against phosphodiesterases to enhance the sperm motility

Satish, Mutyala and Sandhya, Kumari and Nitin, Kulhar and Yashas Kiran, Ninjoor and Aleena, Babu and Satish Kumar, Adiga and Guruprasad, Kalthur and Rajakumara, Eerappa (2022) Computational, biochemical and ex vivo evaluation of xanthine derivatives against phosphodiesterases to enhance the sperm motility. Journal of Biomolecular Structure and Dynamics. pp. 1-11. ISSN 0739-1102

Full text not available from this repository. (Request a copy)

Abstract

Enhancing sperm motility in vitro has immensely benefited assisted conception methods. Phosphodiesterases (PDE) break the second messenger cAMP, and therefore, inhibition of their catalytic activity enhances the sperm motility through maintaining cAMP homeostasis in sperm. In view of identifying the molecules that could inhibit PDE functioning in spermatozoa, we aimed to evaluate the phosphodiesterase inhibitors (PDEI) - xanthine derivatives - acefylline, dyphylline and proxyphylline to repurpose them for assisted reproductive technology. These are available in the market as pharmaceutical agents to treat mainly respiratory system diseases. Based on the structure guided in silico studies, we predicted that these molecules bind to the cAMP binding catalytic pocket of PDE enzymes, and further molecular dynamics simulation analysis indicated that these molecules form the stable complexes. Isothermal titration calorimetry studies revealed that acefylline has better affinity towards PDE4A, PDE4D and PDE10A, when compared to dyphylline and proxyphylline. In addition, ex vivo studies corroborated in vitro binding studies that acefylline has much superior sperm motility enhancement property on human ejaculated spermatozoa and mouse testicular spermatozoa compared to dyphylline and proxyphylline. Communicated by Ramaswamy H. Sarma. © 2022 Informa UK Limited, trading as Taylor & Francis Group.

[error in script]

IITH Creators:

IITH Creators	ORCiD
Rajakumara, Eerappa	https://orcid.org/0000-0002-9341-0070

Item Type:

Article

Additional Information:

E.R. thanks the Department of Biotechnology (DBT) and the Science and Engineering Research Board, the Department of Science and Technology, the Government of India for the Ramalingaswami re-entry fellowship and the Early Career Research Award, respectively. M.S. and K.N. thank the Ministry of Human Resource Development, Government of India for the fellowship.

Uncontrolled Keywords:

assisted reproductive technology; isothermal titration calorimetry; Phosphodiesterase inhibitors; sperm motility; xanthine derivatives

Subjects:

Others > Biotechnology

Divisions:

Department of Biotechnology

Depositing User:

. LibTrainee 2021

Date Deposited:

11 Oct 2022 09:41

Last Modified:

11 Oct 2022 09:41