In-vitro metabolic inhibition and antifertility effect facilitated by membrane alteration: Search for novel antifertility agent using nifedipine analogues

In search of non-hormonal male contraceptives, analogues of nifedipine, which causes reversible infertility, have been synthesized and their interaction at molecular level with model membrane has been probed. Analogues act differently with respect to their antifertility action. This is achieved by altering the cell metabolism thereby directly affecting the motility which is responsible for fertility. Secondly, these drugs bind differently to the interior of the cell-membrane affecting the membrane fluidity, architecture and dynamics. Sulfasalazine and D4 interact to a larger extent and alter the lipid bilayer phase to a hexagonal. D1, D2 and D3 do not have considerable effect. D4 is the most promising candidate as a lead compound for the development of novel non-hormonal male antifertility agents.

Graphical abstractEffect of nifedipine analogues on sperm fertility has been demonstrated by monitoring polymorphism, dynamics and thermotropic behavior of the membrane-drug system and by monitoring anaerobic glycolysis of spermatozoa in real time.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Search for novel non-hormonal, reversible male contraceptive. ► Real time anaerobic glycolysis is monitored in presence of nifedipine analogues. ► Analogues affect cell metabolism, motility and thereby fertility. ► Analogues bind and affect membrane fluidity, architecture and dynamics differently.