Abstract
Novel 5-nitro-1, 3-benzoxazole derivatives (2–8) are synthesized from 5-nitro-1,3-benzoxazole-2-thiol 1. The newly synthesized compounds are characterized by analytical 1H NMR, 13C NMR, LC–MS mass spectrometry, and elemental analysis. All compounds are screened for in vitro anthelmintic activities. In correlation to in vitro anthelmintic activity, all compounds are subjected to molecular docking studies for the inhibition of β-tubulin, target protein elite to the parasites. Compounds 1 and 4 have emerged as potent anthelmintic molecules. The binding energy and hydrogen bonds formed with the surrounding amino acids are in good agreement with predicted binding affinities obtained by molecular docking studies as verified by anthelmintic studies. The compound 5 has showed minimum binding energy with a hydrogen bond, and molecules 1, 4, 6, and 7 have good affinity toward the active pocket with two or more hydrogen bonds respectively, thus they may be considered as good inhibitor of β-tubulin.
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References
Ajaiyeoba EO, Onocha PA, Olarenwaju OT (2001) In vitro anthelmintic properties of Buchholzia coriaceae and Gynandropsis gynandra extract. Pharm Biol 39:217–220
Binkowski TA, Naghibzadeg S, Liang J (2003) CASTp computed atlas of surface topography of proteins. Nucleic Acid Res 31:3352–3355
Cox FEG (2002) History of human parasitology. Clin Microbiol Rev 15:595–612
Dash GK, Suresh P, Kar DM, Ganpaty S, Panda SB (2002) Evaluation of Evolvulus alsinoides Linn. for anthelmintic and antimicrobial activities. J Nat Rem 2:182–185
De Clercq D, Sacko M, Behnke J, Gilbert F, Dorny P, Vercruysse J (1997) Failure of mebendazole in treatment of human hookworm infections in the southern region of Mali. Am J Trop Med Hyg 57:25–30
Deev SL, Shenkarev ZO, Shestakova TS, Chupakhin ON, Rusinov VL, Arseniev AS (2010) Selective 15N-labeling and analysis of 13C–15N J couplings as an effective tool for studying the structure and azide–tetrazole equilibrium in a series of tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines. J Org Chem 75:8487–8497
Friedman PA, Platzer EG (1978) Interaction of anthelmintic benzimidazoles and benzimidazole derivatives with bovine brain tubulin. Biochim Biophys Acta 544:605–614
Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity—a rapid access to atomic charges. Tetrahedron 36:3219–3288
Hotez PJ (2013) Forgotten people and forgotten diseases, the neglected tropical diseases and their impact on global health and development. Clin Infect Dis 57:1793–1794
Hotez PJ, Ottesen E, Fenwick A, Molyneux D (2006) The neglected tropical diseases: the ancient afflictions of stigma and poverty and the prospects for their control and elimination. Adv Exp Med Biol 582:23–33
Ismail M, Metwally A, Farghaly A, Bruce J, Tao L-F, Bennett JL (1996) Characterization of isolates of Schistosoma mansoni from Egyptian villagers that tolerate high doses of praziquantel. Am J Trop Med Hyg 55:214–218
Kohler P, Bachmann R (1981) Intestinal tubulin as possible target for chemotherapeutic action of mebendazole in parasitic nematodes. Mol Biochem Parasitol 4:325–336
Kontoyianni M, McClellan LM, Sokol GS (2004) Evaluation of docking performance: comparative data on docking algorithms. J Med Chem 47:558
Lacey E (1988) The role of the cytoskeletal protein, tubulin, in the mode of action and mechanism of drug resistance to benzimidazoles. Int J Parasitol 18:885–936
Reynoldson JA, Behnke JM, Pallant LJ, Macnish MG, Gilbert F, Giles S, Spargo RJ, Thompson RCA (1997) Failure of pyrantel in treatment of human hookworm infections (Ancylostoma duodenale) in the Kimberley region of North West Australia. Acta Trop 68:301–312
Robinson MW, McFerran N, Trudgett A, Hoey L, Fairweather I (2004) A possible model of benimidazole binding to β-tubulin disclosed by invoking an inter-domain movement. J Mol Graph Model 23:275–284
Satyendra RV, Vishnumurthy KA, Vagdevi HM, Rajesh KP, Manjunatha H, Shruthi A (2011) Synthesis, in vitro antioxidant, anthelmintic and molecular docking studies of novel dichloro substituted benzoxazole-triazolo-thione derivatives. Eur J Med Chem 46:3078–3084
Shivkumar YM, Kumar VL (2003) Anthelmintic activity of latex of Calotropis procera. Pharma Biol 41:263–265
Stelma F, Talla I, Sow S, Kongs A, Niang M, Polman K, Deelder AM, Gryseels B (1995) Efficacy and side effects of praziquantel in an epidemic focus of Schistosoma mansoni. Am J Trop Med Hyg 63:167–170
Van Wyk JA, Malan FS, Randles JL (1997) How long before resistance makes it impossible to control some field strains of Haemonchus contortus in South Africa with any of the modern anthelmintics. Vet Parasitol 70:111–122
Vigar Z (1984) Atlas of medical parasitology, 2nd edn. P. G. Publishing House, Singapore, p 242
Waller PJ, Dash KM, Barger A, Le Jambre LF, Plant J (1995) Anthelmintic resistance in nematode parasites of sheep: learning from the Australian experience. Vet Rec 136:411–413
Waller PJ, Echevarria F, Eddi C, Maciel S, Nari A, Hansen JW (1996) The prevalence of anthelmintic resistance in nematode parasites of sheep in Southern Latin America: general overview. Vet Parasitol 62:181–187
Wang R, Lu Y, Wang S (2003) Comparative evaluation of 11 scoring functions for molecular docking. J Med Chem 46:2287
Acknowledgments
The authors are thankful to BASF India Ltd., Mangalore, India for their invaluable support. The authors are also thankful to Head, Department of Inorganic and Physical Chemistry, IISc, Bangalore, Innovation center, Manipal Institute of technology, Manipal, for providing spectral data. DBL thank Jain University for the constant encouragement given to progress in research.
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The authors declare that they have no conflicts of interest with respect to the content of the manuscript.
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Satyendra, R.V., Vishnumurthy, K.A., Vagdevi, H.M. et al. Synthesis, in vitro anthelmintic, and molecular docking studies of novel 5-nitro benzoxazole derivatives. Med Chem Res 24, 1342–1350 (2015). https://doi.org/10.1007/s00044-014-1207-6
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DOI: https://doi.org/10.1007/s00044-014-1207-6