Mechanism of action of some acrylophenones, quinolines and dithiocarbamate as potent, non-detergent spermicidal agents

Maikhuri, Jagdamba P.; Dwivedi, Anil Kumar; Dhar, J.D.; Setty, B.S.; Gupta, Gopal

doi:10.1016/s0010-7824(03)00022-2

Cited by 32 publications

(23 citation statements)

References 29 publications

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“…Hence, there is a need for designed synthesis of potent, more specifically acting spermicidal microbicides for prophylactic contraception. Our enduring attempts to target human sperm through differently guided molecules against various functional moieties yielded some very promising structures (7,12,(14)(15)(16)(17)(18)(19)(20)22), but the two most promising spermicides (14,16) were weakly microbicidal against Trichomonas vaginalis (15).…”

mentioning

confidence: 99%

Novel Trichomonacidal Spermicides

Jain

Lal

Kumar

et al. 2011

Antimicrob Agents Chemother

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Metronidazole, the U.S. Food and Drug Administration-approved drug against trichomoniasis, is nonspermicidal and thus cannot offer pregnancy protection when used vaginally. Furthermore, increasing resistance of Trichomonas vaginalis to 5-nitro-imidazoles is a cause for serious concern. On the other hand, the vaginal spermicide nonoxynol-9 (N-9) does not protect against sexually transmitted diseases and HIV in clinical situations but may in fact increase their incidence due to its nonspecific, surfactant action. We therefore designed dually active, nonsurfactant molecules that were capable of killing Trichomonas vaginalis (both metronidazole-susceptible and -resistant strains) and irreversibly inactivating 100% human sperm at doses that were noncytotoxic to human cervical epithelial (HeLa) cells and vaginal microflora (lactobacilli) in vitro. Anaerobic energy metabolism, cell motility, and defense against reactive oxygen species, which are key to survival of both sperm and Trichomonas in the host after intravaginal inoculation, depend crucially on availability of free thiols. Consequently, molecules were designed with carbodithioic acid moiety as the major pharmacophore, and chemical variations were incorporated to provide high excess of reactive thiols for interacting with accessible thiols on sperm and Trichomonas. We report here the in vitro activities, structureactivity relationships, and safety profiles of these spermicidal antitrichomonas agents, the most promising of which was more effective than N-9 (the OTC spermicide) in inactivating human sperm and more efficacious than metronidazole in killing Trichomonas vaginalis (including metronidazole-resistant strain). It also significantly reduced the available free thiols on human sperm and inhibited the cytoadherence of Trichomonas on HeLa cells. Experimentally in vitro, the new compounds appeared to be safer than N-9 for vaginal use.

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mentioning

confidence: 99%

Novel Trichomonacidal Spermicides

Jain

Lal

Kumar

et al. 2011

Antimicrob Agents Chemother

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“…Lipid peroxidation can have a negative impact on both sperm motility and fertilization capacity (Aitken & Curry, 2011). Nonoxynol-9 affects the structural and the functional integrity of spermatozoa, and also causes increased lipid peroxidation (Maikhuri et al, 2003). On the contrary, a single administration of anandamide causes lipid peroxidation in the brain of rats (Costa & Colleoni, 2000), and this compound is also known to inhibit spermatozoa capacitation and the acrosome reaction (Rossato, 2008;Rossato et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Effects ofHeliopsis longipesethanolic extract on mouse spermatozoain vitro

Martinez-Loredo

Izquierdo-Vega

Cariño-Cortés

et al. 2015

Pharmaceutical Biology

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Context: Heliopsis longipes (A. Gray) Blake (Asteraceae), a plant native to Mexico, is used in traditional medicine as analgesic and microbicide. The main component in the H. longipes ethanolic extract (HLEE) is affinin, as determined by HPLC/UV-visible and NMR measurement. To date, there is no documented evidence on the spermicidal activity of this extract. Objective: The objective of this study was to assess in vitro the effectiveness of HLEE as spermicide. Materials and methods:The spermicidal activity of HLEE was evaluated by the Sander-Cramer assay. Spermatozoa were incubated for 20 s with HLEE in concentrations ranging from 75 to 2000 mg/mL to determine the minimum effective concentration (MEC) value. The 50% effective concentration (EC 50 ) of HLEE was estimated by assaying serial dilutions from the MEC. Additionally, sperms were incubated with 125, 250, or 500 mg/mL of HLEE to evaluate the viability and the integrity of sperm membrane. Lipid peroxidation was assessed by the thiobarbituric acid reactive substances assay. Results: HLEE caused an inhibition of 100% in spermatozoa motility at a MEC value of 2000 mg/mL; the EC 50 value was 125 mg/mL. Additionally, exposure to HLEE at 125, 250, or 500 mg/mL for 30 min decreased sperm viability to 27%, 8%, and 2% of the control value, respectively, and significantly increased the percentage of sperms with structurally disorganized membrane. HLEE also increased significantly the level of lipid peroxidation in sperms with respect to controls. Discussion and conclusion: The results demonstrate the spermicidal activity of HLEE in vitro and suggest that this action is caused by oxidative damage and alterations in the spermatozoal membrane.

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“…It is advocated to be totally safe and easy to use. It is intended for post-coital use 46 . Raghuvanshi et al developed a spermicide compound, called Praneem polyherbal, featuring anti-microbial traits, from the pericarp of fruit of S. mukorossi, leaves of Azadirachta indica, and oil of Mentha citrata.…”

Section: Anti-asthmatic Activitymentioning

confidence: 99%

Medicinal Plants of the Genus Sapindus (Sapindaceae) - A Review of Their Botany, Phytochemistry, Biological Activity and Traditional Uses

Goyal

2014

J. Drug Delivery Ther.

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Mechanism of action of some acrylophenones, quinolines and dithiocarbamate as potent, non-detergent spermicidal agents

Cited by 32 publications

References 29 publications

Novel Trichomonacidal Spermicides

Novel Trichomonacidal Spermicides

Effects ofHeliopsis longipesethanolic extract on mouse spermatozoain vitro

Medicinal Plants of the Genus Sapindus (Sapindaceae) - A Review of Their Botany, Phytochemistry, Biological Activity and Traditional Uses

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