Synthesis and Structure-Activity Relationships of Novel Neocryptolepine Derivatives

doi:10.1007/s40242-017-6502-6

Abstract

Abstract:

Herein we reported the synthesis of a novel series of neocryptolepine(5-methyl-5H-indolo[2,3-b]quinoline) derivatives containing different substituents at C11 using methyl 1H-indole-3-carboxylate and N-methylaniline as starting material. The target 21 compounds were evaluated for their antibacterial activity in vitro against gram-positive bacteria(B. subtilis and S. aureus) and gram-negative bacteria(E. coli and vS. typhi). Almost all the tested compounds showed moderate to high activities against the four bacterial strains at the minimum inhibitory concentrations(MICs) of 1-10 μg/mL. The obtained results suggest that part of the novel synthetic neocryptolepine derivatives exhibit significant antibacterial effect against all the tested organisms.

Key words: Neocryptolepine, Indoloquinoline, Antibacterial

Ahmed A. EL-GOKHA, Nader M. BOSHTA, Mona K. ABO HUSSEIN, Ibrahim EL-T. EL SAYED. Synthesis and Structure-Activity Relationships of Novel Neocryptolepine Derivatives[J]. Chemical Research in Chinese Universities, 2017, 33(3): 373-377.

References

[1] Butler M. S., J. Nat. Prod., 2004, 67, 2141
[2] Cimanga K., Bruyne T. D., Pieters L., Claeys M., Vlietinck A., Tet-rahedron Lett., 1996, 37, 1703
[3] El Sayed I., Ramzy F., William S., El Bahanasawy M., Abdel-Staar M. M., Med. Chem. Res., 2012, 21, 4219
[4] El Sayed I. E., Veken P. V., Dhooghe L., Hostyn S., van Baelen G., Lemière G., Maes B. U. W., Cos P., Maes L., Joossens J., Haemers A., Pieters L., Augustyns K., J. Med. Chem., 2009, 52, 2979
[5] Jonckers T. H. M., van Miert S., Kanyanga C., Bailly C., Colson P., de Pauw-Gillet M. C., van den Heuvel H., Claeys M., Lemiere F., Esmans E. L., Rozenski J., Quirijnen L., Maes L., Dommisse R., Lemière G. L. F., Vlietinck A., Pieters L., J. Med. Chem., 2002, 45, 3497
[6] Lavrado J., Moreira R., Paulo A., Curr. Med. Chem., 2010, 17, 2348
[7] Lu W. J., ?witalska M., Wang L., Yonezawa M., El Sayed I. E., Wietrzyk J., Inokuchi T., Med. Chem. Res., 2013, 22, 4492
[8] Lu W. J., Wicht K. J., Wang L., Imai K., Mei Z. W., Kaiser M., El Sayed I. E., Egan T. J., Inokuchi T., Eur. J. Med. Chem., 2013, 64, 498
[9] Prakash T. P., Perunninakulath S. P., Santosh G. T., Curr. Org. Chem., 2011, 15, 1036
[10] Mei Z. W., Wang L., Lu W. J., Pang C. Q., Maeda T., Peng W., Kaiser M., El Sayed I. E., Inokuchi T., J. Med. Chem., 2013, 56, 1431
[11] Wang N., Imai K., Pang C. Q., Wang M. Q., Yonezawa M., Zhang Y., Nokami J., Inokuchi T., Bull. Chem. Soc. Jpn., 2013, 86, 864
[12] Wang L., ?witalska M., Mei Z. W., Lu W. J., Takahara Y., Feng X. W., Sayed I. E., Wietrzyk J., Inokuchi T., Bioorg. Med. Chem., 2012, 20, 4820
[13] Xu Y. J., Pieters L., Mini. Rev. Med. Chem., 2013, 13, 1056
[14] Paulo A., Pimentel M., Viegas S., Pires I., Duarte A., Cabrita J., Gomes E. T., J. Ethnopharmacol., 1994, 44, 73
[15] Paulo A., Duarte A., Gomes E. T., J. Ethnopharmacol., 1994, 44, 127
[16] Sawer I. M., Brown M. W., Ford J. L., J. Appl. Bacteriol., 1995, 79, 314
[17] Cimanga K., de Bruyne T., Pieters L., Totte J., Tona L., Kambu K., van den Berghe D., Vlietinck A. J., Phytomedicine, 1998, 5, 209
[18] Mills-Robertson F. C., Aboagye F. A., Duker-Eshun G., Kaminta S., Agbeve S., Afr. J. Pharm. Pharmacol., 2009, 3, 476
[19] Mills-Robertson F. C., Tay S. C., Duker-Eshun G., Walana W., Badu K., Ann. Clin. Microbiol. Antimicrob., 2012, 11, 16
[20] Molina A., Vaquero J. J., Garcia-Navio J. L., Alvarez-Builla J., Pascula-Terasa B., Gago F., Rodrigo M. M., Ballestros M., J. Org. Chem., 1996, 61, 5587
[21] Guittat L., Alberti P., Rosu F., van Miert S., Thetiot E., Pieters L., Gabelica V. E., Pauw D., Ottaviani A., Riou J. F., Mergny J. L., Biochimie, 2003, 85, 535
[22] Poole K., J. Pharm. Pharmacol., 2001, 53, 283
[23] Costerton J. W., Cheng K. J., J. Antimicrob. Chemother., 1975, 1, 363 and references cited therein
[24] Cushnie T. P., Lamb A. J., Int. J. Antimicrob. Agents, 2005, 26, 343
[25] El-Essawy F. A., Boshta N. M., Alotaibi M. A., Elsayed M. S., Tarabees R. E., Saleh A., Res. Chem. Intermed., 2016, 42, 8157
[26] El-Essawy F. A., Boshta N. M., El-Sawaf A. K., Nassar A. A., Kha-lafallah M. S., Chem. Res. Chinese Universities, 2016, 32(6), 967
[27] El Sayed I., El Kosy S. M., Hawata M. A., El Gokha A., Tolan A., Abd El-Sattar M., J. Am. Sci., 2011, 7, 357
[28] Bailly C., Laine W., Baldeyrou B., de Pauw-Gillet M. C., Colson P., Houssier C., Cimanga K., van Miert S., Vlietinck A., Pieters L., Anti-Cancer Drug Des., 2000, 15, 191
[29] Wang L., Lu W. J., Odawara T., Misumi R., Mei Z. W., Peng W., El-Sayed I. E. T., Inokuchi T., J. Heterocyclic. Chem., 2014, 51, 1106
[30] Peczyńska-Czoch W., Pognan F., Kaczmarek ?., Boratyński J., J. Med. Chem., 1994, 37, 3503
[31] Osiadacz J., PeczynÄska-Czoch W., Kaczmarek O. A., 6th Interna-tional Symposium on Molecular Aspects of Chemotherapy. 9-12 July, 1997, GdanÄsk, Poland
[32] Kaczmarek L., Peczynska-Czoch W., Osiadacz J., Mordarski M., Sokalski W. A., Boratynski J., Marcinkowska E., Glazman-Kusnierczyk H., Radzikowski C., Bioorg. Med. Chem., 1999, 7, 2457
[33] Hsueh P. R., Chang J. C., Teng L. J., Yang P. C., Ho S. W., Hsieh W. C., Luh K. T., J. Clin. Microbiol., 1997, 35, 1021