Substituted acrylophenones and related mannich bases as possible spermicides and inhibitors of HIV envelope glycoprotein–CD4 interaction

Kumaria, Niharika; Dwivedi, Anil Kumar; Maikhuri, Jagdamba P.; Gupta, Gopal; Habib, Saman; Dhar, J.D.; Singh, Satyawan

doi:10.1016/s0223-5234(01)01292-2

Cited by 13 publications

(5 citation statements)

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“…Synthesis and evaluation of novel, non-detergent structures at this institute has led to the discovery of several prototypes with potent spermicidal activity. These include acrylophenones (Kumaria et al, 2002;Maikhuri et al, 2003), dithiocarbamates (Tripathi et al, 1996), quinines (Maikhuri et al, 2003), anysylidines, thymols and isoxazoles/isoxazolines (Srivastava et al, 1999). In isoxazoline and isoxazole derivatives reported by us previously, we have found a potent spermicidal response including anti-HIV activity in a few derivatives (Srivastava et al, 1999).…”

Section: Introductionsupporting

confidence: 54%

Discovery of substituted isoxazolecarbaldehydes as potent spermicides, acrosin inhibitors and mild anti-fungal agents

et al. 2005

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Section: Introductionsupporting

confidence: 54%

Discovery of substituted isoxazolecarbaldehydes as potent spermicides, acrosin inhibitors and mild anti-fungal agents

et al. 2005

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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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“…Compounds 8 and 9 were synthesized by the treatment of 4 with 4-[2-(piperidin-1-yl)ethoxy]acetophenone [28] and 4-[2-(pyrrolidin-1-yl)ethoxy]acetophenone respectively. Reaction of 4-hydroxyacetophenone and 3-chloro-N,N-dimethylpropanamine followed by the addition of 4 under basic conditions afforded compound 10.…”

Section: Chemistrymentioning

confidence: 99%

“…Compound 9 was obtained from 4 and 4-[2-(piperidin-1-yl) ethoxy]acetophenone [28] as described for 7 in 63% yield. Mp.…”

Section: (E)-3-[3-(4-methoxyphenyl)quinolin-2-yl]-1-{4-[2-(pyrrolidinmentioning

confidence: 99%

Discovery of 3-phenylquinolinylchalcone derivatives as potent and selective anticancer agents against breast cancers

Tseng

Tzeng

Hsu

et al. 2015

European Journal of Medicinal Chemistry

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Substituted acrylophenones and related mannich bases as possible spermicides and inhibitors of HIV envelope glycoprotein–CD4 interaction

Cited by 13 publications

References 4 publications

Discovery of substituted isoxazolecarbaldehydes as potent spermicides, acrosin inhibitors and mild anti-fungal agents

Discovery of substituted isoxazolecarbaldehydes as potent spermicides, acrosin inhibitors and mild anti-fungal agents

Novel Trichomonacidal Spermicides

Discovery of 3-phenylquinolinylchalcone derivatives as potent and selective anticancer agents against breast cancers

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