Skip to main content

Advertisement

SpringerLink
Log in

Amberlite IRA 402(OH)-mediated synthesis and evaluation of fused tricyclic quinolinium salts as potent non-detergent type microbicidal spermicides

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Fused tricyclic oxazaquinolinium salts were synthesized using Amberlite IRA 402(OH) in water and assessed for their sperm-immobilizing efficacy in vitro by modified Sander–Cramer test followed by double fluoroprobe staining of rat sperm. Out of 11 derivatives 3 showed potent spermicidal effect. The mode of spermicidal action was assessed by (a) Hypoosmotic swelling tests, (b) Lipid peroxidation studies, and (c) scanning electron microscopy. Antimicrobial efficacies of the potent derivatives, assessed by disc diffusion as well as by agar and broth dilution methods using human isolates of bacteria and fungi, revealed their moderate antimicrobial potential. The compounds, found to be nontoxic to rabbit erythrocytes by haemolytic assay, may be exploited as microbicidal spermicides.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Aitken RJ, Buckingham D, Harkiss D (1993) Use of xanthine oxidase free radical generating system to investigate the cytotoxic effects of reactive oxygen species on human spermatozoa. J Reprod Fertil 97:441–450

    Article  CAS  PubMed  Google Scholar 

  • Banerjee M, Kumar S, Paira R, Ghosh S, Karmokar S, Mondal N.B (2013) Synthesis and characterization of furo[3,2-h]quinoliniums as potent non-detergent spermicides. BSP Letters in Drug Design and Discovery, in press

  • Bharitkar YP, Banerjee M, Kumara S, Paira R, Meda R, Kuotsub K, Mondal Nirup B (2013) Search for a potent microbicidal spermicide from the isolates of Shorea robusta resin. Contraception 88:133–140

    Article  CAS  PubMed  Google Scholar 

  • Bhowal SK, Lala S, Hazra A, Paira P, Banerjee S, Mondal NB, Chakrabarty S (2008) Synthesis and assessment of fertility regulating potential of 2-(2″-chloroacetamidobenzyl)-3-(3′-indolyl) quinoline in adult rats as a male contraceptive agent. Contraception 77:214–222

    Article  CAS  PubMed  Google Scholar 

  • Chattopadhyay D, Dastidar SG, Chakrabarty AN (1988) Antibacterial property of methdilazine and its synergism with antibiotics and some chemotherapeutic agents. Arzneim Forsch 38(II):869–872

    CAS  Google Scholar 

  • Chattopadhyay D, Mukherjee T, Pal P, Saha B, Bhadra R (1998) Altered membrane permeability as the basis of bactericidal action of methdilazine. J Antimicrob Chemother 42:83–86

    Article  CAS  PubMed  Google Scholar 

  • CLSI (2009) Methods for antifungal disk diffusion susceptibility testing of filamentous fungi; proposed guideline. CLSI documents M51-P. Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  • CLSI (2012) Performance standards for antimicrobial disk susceptibility tests; approved standard—eleventh edition M02-A11. Clinical and Laboratory Standards Institute, Wayne

    Google Scholar 

  • D’Cruz OJ, Shih MJ, Yiv SH, Chen CL, Uckun FM (1999) Synthesis, characterization and preclinical formulation of a dual-action phenyl phosphate derivative of bromo-methoxy zidovudine (compound WHI-07) with potent anti-HIV and spermicidal activities. Mol Hum Reprod 5:421–432

    Article  PubMed  Google Scholar 

  • Doncel GF (2006) Exploiting common targets in human fertilization and HIV infection: development of novel contraceptive microbicides. Hum Reprod Update 12:103–117

    Article  CAS  PubMed  Google Scholar 

  • Flajshans M, Cosson J, Rodina M, Linhart O (2004) The application of image cytometry to viability assessment in dual fluorescence-stained fish spermatozoa. Int J Cell Biol 28:955–959

    Article  CAS  Google Scholar 

  • Hawes SE, Hillier SL, Benedetti J, Stevens CE, Koutsky LA, Hanssen P, Holmes K (1996) Hydrogen peroxide producing lactobacilli and acquisition of vaginal infections. J Infec Dis 174:1058–1063

    Article  CAS  Google Scholar 

  • ICPD ‘94: summary of the programme of action. International conference on population and development, United Nations, 1995. Available from http://www.un.org/ecosocdev/geninfo/populatin/icpd.htm. Accessed 5–13 Sep 1994

  • Jain RK, Maikhuri JP, Kiran KSTVS, Sharma VL, Dwivedi AK, Mitra K, Bajpai VK, Gupta G (2007) Novel disulphide esters of carbothioic acid as potent, non-detergent spermicides with low toxicity to Lactobacillus and HeLa cells in vitro. Hum Reprod 22:708–716

    Article  CAS  PubMed  Google Scholar 

  • Jayendran RS, Van der Ven HH, Perag-Pelaez M, Crab BG, Zaneveld LJD (1984) Development of an assay to assess the functional integrity of the human sperm membrane and its relationship to other semen characteristics. J Reprod Fertil 70:219–228

    Article  Google Scholar 

  • Kanwar U, Anand RJK, Sanyal SN (1993) The effect of nifedipine, a calcium channel blocker, on human spermatozoal function. Contraception 48:453–470

    Article  CAS  PubMed  Google Scholar 

  • Kempf C, Jentsch P, Barre-Sinoussi FB, Poirier B, Morgenthaler JJ, Morell A, Germann D (1991) Inactivation of human immunodeficiency virus (HIV) by low pH and pepsin. J Acquir Immune Defic Syndr 4:828–830

    CAS  PubMed  Google Scholar 

  • Khillare B, Shrivastav TG (2003) Spermicidal activity of Azadirachta indica 528(neem) leaf extract. Contraception 68:225–229

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Biswas S, Mandal D, Roy HN, Chakraborty S, Kabir SN, Banerjee S, Mondal NB (2007) Chenopodium album seed extract:a potent sperm-immobilizing agent both in vitro and in vivo. Contraception 75:71–78

    Article  PubMed  Google Scholar 

  • Kumar S, Chatterjee R, Dolai S, Adak S, Kabir SN, Banerjee S, Mondal NB (2008) Chenopodium album seed extract induced sperm cell death: exploration of a plausible pathway. Contraception 77:456–462

    Article  PubMed  Google Scholar 

  • Kumar S, Naskar S, Hazra A, Sarkar S, Mondal NB, Banerjee S (2009) Evaluation of spermicidal potential of labdane diterpenes from Andrographis paniculata. Int J Biol Chem Sci 3:628–636

    Google Scholar 

  • Kumar S, Biswas S, Banerjee S, Mondal NB (2011) Evaluation of safety margins of Chenopodium album seed decoction: 14-day subacute toxicity and microbicidal activity studies. Reprod Biol Endocrin 9:102–110

    Article  Google Scholar 

  • Martin HL, Richardson BA, Nyange PM, Lavreys L, Hillier SL, Chohan B, Mandaliya K et al (1999) Vaginal lactobacilli, microbial flora and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis 180:1863–1868

    Article  CAS  PubMed  Google Scholar 

  • Paira P, Hazra A, Kumar S, Paira R, Sahu KB, Naskar S, Saha P, Mondal S, Maity A, Banerjee S, Mondal NB (2009) Efficient synthesis of 3,3-diheteroaromatic oxindole analogues and their in vitro evaluation for spermicidal potential. Bioorg Med Chem Lett 19:4786–4789

    Article  CAS  PubMed  Google Scholar 

  • Paira R, Paira P, Maity A, Mondal S, Hazra A, Sahu KB, Naskar S, Saha P, Banerjee M, Mondal NB (2010) Amberlite IRA 402(OH): an efficient mediator for the exclusive synthesis of fused tricyclic oxaza quinolinium salts. Tetrahedron Lett 51(24):513200–513204

    Article  Google Scholar 

  • Pal D, Chakraborty P, Ray HN, Pal BC, Mitra D, Kabir SN (2009) Acaciaside-B-enriched fraction of Acacia auriculiformis is a prospective spermicide with no mutagenic property. Reproduction 138:453–462

    Article  CAS  PubMed  Google Scholar 

  • Palit P, Paira P, Hazra A, Banerjee S, Das Gupta A, Dastidar SG, Mondal NB (2009) Phase transfer catalysed synthesis of bis-quinolines: antileishmanial activity in experimental visceral Leishmaniasis and in vitro antibacterial evaluation. Eur J Med Chem 44:845–853

    Article  CAS  PubMed  Google Scholar 

  • Pape W, Hoppe U (1991) In vitro methods for the assessment of primary local effects of topically applied preparations. Skin Pharmacol 4:205–212

    Article  CAS  PubMed  Google Scholar 

  • Pape W, Pfannenbecker U, Hoppe U (1987) Validation of the red blood cell test system as in vitro assay for the rapid screening of irritation potential of surfactants. Mol. Toxicol 88:525–536

    Google Scholar 

  • Ray S, Sadhukhan PK, Mondal NB, Mahato SB, Majumder HK (1997) Dual Inhibition of DNA Topoisomerases of Leishmania donovani by Novel Indolyl Quinolines. Biochem Biophys Res Commun 230:171–175

    Article  CAS  PubMed  Google Scholar 

  • Renner R (1997) European bans on surfactant trigger transatlantic debate. Environ Sci Technol 31:A316–A320

    Article  Google Scholar 

  • Roddy RE, Zeking L, Ryan KA, Tamoufe U, Weir SS, Wong EL (1998) A controlled trial of nonoxynol 9 film to reduce male-to-female transmission of sexually transmitted diseases. N Engl J Med 339:504–510

    Article  CAS  PubMed  Google Scholar 

  • Sahu KB, Banerjee M, Ghosh S, Maity A, Mondal S, Paira R, Hazra A, Karmakar S, Samanta A, Mondal NB (2013) I2 catalyzed Friedel-Crafts alkylation reaction of substituted anilines with ninhydrin: formation of novel products and their antimicrobial evaluation. Med Chem Res 22:2023–2037

    Article  CAS  Google Scholar 

  • Shah V, Doncel GF, Seyoum T, Eaton KM, Zalenskaya I, Hagver R, Azim A, Gross R (2005) Sophorolipids, Microbial glycolipids with anti-human immuno-deficiency virus and sperm-immobilizing activities. Antimicrob Agents Chemother 49:4093–4100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Sharma SK, SaiRam M, Ilvazhagan G, Devendra K, Shivaji SS, Selvamurthy W (1996) Mechanism of action of NIM-76: a novel vaginal contraceptive from neem oil. Contraception 54:373–378

    Article  CAS  PubMed  Google Scholar 

  • Singh KK, Parmar S, Tatke PA (2012) Contraceptive efficacy and safety of HerbOshield™ vaginal gel in rats. Contraception 85:122–127

    Article  CAS  PubMed  Google Scholar 

  • Thiele B, Gunther K, Schwuger M (1997) Alkylphenol ethoxylates trace analysis and environmental behavior. Chem Rev 97:3247–3272

    Article  CAS  PubMed  Google Scholar 

  • United Nations Population Fund (2011) State of the world population 2011. New York: UNFPA. Available from http://www.unfpa.org/swp/. Accessed 17 Oct 2011

  • Va′squez A, Jakobsson T, Ahrne S, Forsum U, Molin G (2002) Vaginal Lactobacillus flora of healthy Swedish women. J Clin Microbiol 40:2746–2749

    Article  Google Scholar 

  • Wang C (2012) History of the Chinese Family Planning Program: 1970–2010. Contraception 85:563–569

    Article  PubMed  Google Scholar 

  • Wilborn WH, Hahn DW, McGuire JJ (1983) Scanning electron microscopy of human spermatozoa after incubation with the spermicide nonoxynol-9. Fertil Steril 39:717–719

    CAS  PubMed  Google Scholar 

  • Yu K, Chien YW (1995) Spermicidal activity-structure relationship of nonoxynol oligomers: physicochemical basis. Int J Pharmaceut. 125:81–90

    Google Scholar 

Download references

Acknowledgments

We would like to thank the Council of Scientific and Industrial Research (CSIR), New Delhi, for financial support in the form of fellowships to M.B. and NBM as Emeritus Scientist. We are indebted to Mr. E. Padmanaban and Mr. K. Sarkar for NMR and mass spectral analysis, Dr S.C. Biswas for providing fluorescence microscope and also to Mr. Muruganandan Thangamuniyandi for SEM. We are thankful to Dr B. Achari, Emeritus Scientist, CSIR, for critical suggestions and encouragement.

Author information

Authors and Affiliations

  1. Chemistry Division, Indian Institute of Chemical Biology, Council of Scientific & Industrial Research, 4 Raja S C Mullick Road, Jadavpur, Kolkata, 700032, India

    Maitreyee Banerjee, Shrabanti Kumar, Rupankar Paira, Shyamal Mondal & Nirup B. Mondal

  2. Department of Pharmaceutical Technology, Jadavpur University, Jadavpur, Kolkata, 700032, India

    Soma Ghosh & Sanmoy Karmokar

  3. Virus Unit, I.D. and B.G. Hospital, Indian Council of Medical Research, 57 Dr. Suresh C Banerjee Road, Beliaghata, Kolkata, 700010, India

    Debprsad Chattopadhyay

  4. Infectious Disease and Immunology Division, Indian Institute of Chemical Biology, Council of Scientific & Industrial Research, 4 Raja S C Mullick Road, Jadavpur, Kolkata, 700032, India

    Rupak K. Bhadra

Authors
  1. Maitreyee Banerjee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shrabanti Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Soma Ghosh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rupankar Paira
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shyamal Mondal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sanmoy Karmokar
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Debprsad Chattopadhyay
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rupak K. Bhadra
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nirup B. Mondal
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nirup B. Mondal.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 1119 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Banerjee, M., Kumar, S., Ghosh, S. et al. Amberlite IRA 402(OH)-mediated synthesis and evaluation of fused tricyclic quinolinium salts as potent non-detergent type microbicidal spermicides. Med Chem Res 23, 1488–1500 (2014). https://doi.org/10.1007/s00044-013-0758-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-013-0758-2

Keywords

Search

Navigation