The synthesis of a novel pentoxifylline derivative with superior human sperm motility enhancement properties

Sandhya Kumari, Sukumar Kotyan, Sinoy Sugunan, G. K. Rajanikant, Kothanahally S.Sharath Kumar, Satish Kumar Adiga, Jagadeesh Prasad Dasappa, Guruprasad Kalthur

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Poor sperm motility is one of the major causes of male infertility and fertilization failure in assisted reproductive technology (ART). Pentoxifylline (PTF), a phosphodiesterase inhibitor (PDEI), has been used previously in ART to enhance sperm motility. However, reports on its adverse effects on sperm function and early embryo development have resulted in a need to find safe alternative molecules. The aim of the present study was to synthesize various structurally modified pentoxifylline (mPTF) compounds and then screen them to determine if they possess a beneficial role in enhancing human sperm motility. A series of 3,7-dimethyl-1-[(6E)-5-oxo-7-aryllhept-6-en-1-yl]-3,7-dihydro-1H-purine-2,6-diones (mPTF1-mPTF6) was synthesized via treating PTF with various arylaldehydes in the presence of alcoholic KOH solution. The structures of the novel compounds were confirmed via Fourier transform infrared spectroscopy (FT-IR) (without the KBr method), 1H-NMR, 13C-NMR, and liquid chromatography (LC)-mass spectrometry studies. These compounds were screened for their human sperm motility enhancement properties. Among the six compounds, 1-[(6E)-7-(6-methoxynaphthyl)-5-oxohept-6-en-1-yl]-3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione (mPTF1) exhibited superior motility enhancement and prolonged survival in vitro in comparison to PTF. The optimum activity of mPTF1 was observed at a concentration that was four times lower (0.25 mM) than the parent compound (1 mM), indicating its increased efficiency. Comparative cytotoxicity and genotoxicity assays revealed that mPTF1 has significantly lower genotoxicity than the parent molecule PTF. Overall, the results indicated that the structural modification of PTF can increase sperm motility and its longevity in vitro. The modification also resulted in reduced genotoxic effects. Therefore, mPTF1 may have better therapeutic potential than the parent compound PTF in ART.

Original languageEnglish
Pages (from-to)1072-1081
Number of pages10
JournalNew Journal of Chemistry
Volume45
Issue number2
DOIs
Publication statusPublished - 14-01-2021

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Materials Chemistry

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