Synthesis and antimicrobial screening of novel 1,3-dioxolanes linked to N-5 of 5H-[1,2,4]triazino[5,6-b]indole-3-thiol

El Sayed Ramadan, Hanaa A. Rasheed, El Sayed H. El Ashry


Synthesis of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-1H-indole-2,3-dione (10) has been achieved by coupling of 1H-indole-2,3-dione (16) with (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (15) in the presence of sodium hydride in dry N,N-dimethylformamide at room temperature in a closed Erlenmeyer flask. Condensation of 10 with hydrazinecarbothioamide in water afforded the thiosemicarbazone derivative 17; its subsequent cyclization with potassium carbonate in water gave the corresponding thione 18 in good yield. The 3-allyl and 3-benzylthio derivatives 20 and 21 were also prepared by alkylating thiol 19 with alkyl halides in aqueous sodium hydroxide or coupling of 3-(allyl/benzylthio)-5H-[1,2,4]triazi­no[5,6-b]indoles (23) and (24) with compound 15 in NaH/ DMF. Compound 20 was isomerized to a mixture of geometrical isomers (E/Z)-5-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-3-(prop-1-en-1-yl)-5H-[1,2,4]triazino[5,6-b]indoles (25) and (26) when carrying 1H and 13C NMR spectra in deuterodimethyl sulfoxide. Structural elucidation of the synthesized compounds was carried out by using FT-IR, 1H NMR, 13C NMR, mass spectrometry, and elemental analysis. The newly synthesized compounds were found to possess moderate inhibitory activity against the fungus Candida albicans compared to clotrimazole as reference control. Compounds 10, 17, 19, 20, 21, 23, and 24 had mean growth inhibition zones (IZ) and minimal inhibitory concentrations (MICs) in the range of 12–15 mm and 31.25–200 μg mL–1, with inhibition levels in 70.58–88.23 %. Compound 19 exhibited moderate activity against Gram-positive bacteria Staphylococcus aureus relative to imipenem as standard drug. All compounds were inactive against Escherichia coli and Pseudomonas aeruginosa.


survey; alkylation; dioxolanes; 1H-indole-2,3-dione; candida albi¬cans

Full Text:

PDF (2,844 kB)


S. E. Kassab, G. H. Hegazy, N. M. Eid, K. M. Amin, A. A. El-Gendy, Nucleosides Nucleotides Nucleic Acids 29 (2010) 72

A. Jarrahpour, D. Khalili, E. De Clercq, C. Salmi, J. M. Brunel, Molecules 12 (2007) 1720

M. Verma, S. N. Pandeya, K. N. Singh, J. P. Stables, Acta Pharm. 54 (2004) 49

A. Gürsoy, N. Karalı, Eur. J. Med. Chem. 38 (2003) 633

T. R. Bal, B. Anand, P. Yogesswari, D. Sriram, Bioorg. Med. Chem. Lett. 15 (2005) 4451

S. G. Cresawn, C. Prins, D. R. Latner, R. C. Condit, Virology 363 (2007) 319

I. Chiyanzu, E. Hansell, J. Gut, P. J. Rosenthal, J. H. Mckerrow, K. Chibale, Bioorg. Med. Chem. Lett. 13 (2003) 3527

L. Sebastian, A. Desai, M. N. Shampur, Y. Perumal, D. Sriram, R. Vasanthapuram, Virology Journal 5 (2008) 64

M. M. Hossain, N. Islam, R. Khan, M. R. Islam, Bangladesh J. Pharmacol. 2 (2007) 66

A. B. Tomchin, A. V. Kropotov, Pharm. Chem. J. 32 (1998) 22

L. J. Wilson, W. B. Choi, T. Spurling, D. C. Liotta, R. F. Schinazi, D. Cannon, G. R. Painter, M. S. Clair, P. A. Furman, Bioorg. Med. Chem. Lett. 3 (1993) 169

D. W. Norbeck, S. Spanton, S. Broder, H. Mitsuya, Tetrahedron Lett. 30 (1989) 6263

W. B. Choi, L. J. Wilson, S. Yeola, D. C. Liotta, R. F. Schinazi, J. Amer. Chem. Soc. 113 (1991) 9377

C. K. Chu, S. K. Ahn, H. O. Kim, J. W. Beach, A. J. Alves, L. S. Jeong, Q. Islam, P. Van Roey, R. F. Schinazi, Tetrahedron Lett. 32 (1991) 3791

E. V. Efimtseva, S. N. Mikhailov, S. V. Meshkov, H. Lonnberg, Acta Chem. Scand. 46 (1992) 1122

A. Mousaad, N. Rashed, E. Ramadan, E. S. H. El Ashry, Spectroscopy Lett. 27 (1994) 677

E. S. H. El Ashry, N. Rashed, H. Abdel Hamid, E. Ramadan, Z. Naturforsch. 52b (1997) 873

N. Rashed, H. Abdel Hamid, E. Ramadan, E. S. H. El Ashry, Nucleosides & Nucleotides 17 (1998) 1373

E. S. H. El Ashry, H. Abdel Hamid, A. Mousaad, E. Ramadan, J. Chem. Res. (M) (2002) 752

D. G. Kim, A. V. Zhuravlyova, Chem. Heterocycl. Comp. 46 (2010) 896

M. Gianella-Borradori, I. Christou, C. J. R. Bataille, R. L. Cross, G. M. Wynne, D. R. Greaves, A. J. Russell, Bioorg. Med. Chem. 23 (2015) 241

S. R. Jain, A. Kar, Planta Med. 20 (4) (1971) 118

H. M. Ericsson, J. C. Sherris, Acta Pathol. Microbiol. Scand B. Microbiol. Immunol. 217 (1971) Suppl 217:1+

B. B. Lohray, B. M. Rajesh, V. Bhushan, Indian J. Chem. 41B (2002) 586

K. Yamada, Y. Yoshiazwa, K. Oh, Molecules 17 (2012) 4460

E. Kohli, R. Arora, R. Kakkar, Can. Chem. Trans 2 (2014) 327


Copyright (c) 2018 J. Serb. Chem. Soc.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

IMPACT FACTOR 0.797 (139 of 171 journals)
5 Year Impact Factor 0,923 (134 of 171 journals)