Synthesis and biological activity of some new 1-benzyl and 1-benzoyl-3-heterocyclic indole derivatives

Open access

Synthesis and biological activity of some new 1-benzyl and 1-benzoyl-3-heterocyclic indole derivatives

Starting from 1-benzyl- (2a) and 1-benzoyl-3-bromoacetyl indoles (2b) new heterocyclic, 2-thioxoimidazolidine (4a, b), imidazolidine-2,4-dione (5a, b), pyrano(2,3-d)imida-zole (8a, b and 9a, b), 2-substituted quinoxaline (11a, b-17a, b) and triazolo(4,3-a)quinoxaline derivatives (18a, b and 19a, b) were synthesized and evaluated for their antimicrobial and anticancer activities. Antimicrobial activity screening performed with concentrations of 0.88, 0.44 and 0.22 μg mm-2 showed that 3-(1-substituted indol-3-yl)quinoxalin-2(1H)ones (11a, b) and 2-(4-methyl piperazin-1-yl)-3-(1-substituted indol-3-yl) quinoxalines (15a, b) were the most active of all the tested compounds towards P. aeruginosa, B. cereus and S. aureus compared to the reference drugs cefotaxime and piperacillin, while 2-chloro-3-(1-substituted indol-3-yl)quinoxalines (12a, b) were the most active against C. albicans compared to the reference drug nystatin. On the other hand, 2-chloro-3-(1-benzyl indol-3-yl) quinoxaline 12a display potent efficacy against ovarian cancer xenografts in nude mice with tumor growth suppression of 100.0 ± 0.3 %.

S. Sondhi, M. Dinodia and A. Kumar, Synthesis, anti-inflammatory and analgesic activity evaluation of some amidine and hydrazone derivatives, Bioorg. Med. Chem. 14 (2006) 4657-4663; DOI: 10.1016/j.bmc.2006.02.014.

M. Radwan, E. Rageb, N. Sabry and S. El-Shenawy, Synthesis and biological evaluation of new-3-substituted indole derivatives as potential and anti-inflammatory and analgesic agents, Bioorg. Med. Chem. 15 (2007) 3832-3841; DOI: 10.1016/j.bmc.2007.03.024.

R. Cao, Q. Chen, X. Hou, H. Chen, H. Guan, Y. Ma, W. Peng and A. Xu, Synthesis, acute toxicities and antitumor effects of novel 9-substituted β-carboline derivatives, Bioorg. Med. Chem. 12 (2004) 4613-4623; DOI: 10.1016/j.bmc.2004.06.038.

A. Kar and F. Attah, Synthesis and pharmacological evaluation of some 4-[(3-indolyl)methy - lene]-2-methyloxazolin-5-one analogs, Indian Drug 29 (1991) 87-90.

R.K. Tiwari, D. Singh, J. Singh, V. Yadav, A.K. Pathak, R. Dabur, A.K. Chhillar, R. Singh, G.L. Sharma, R. Chandraa and A.K. Verma, Synthesis and antibacterial activity of substituted 1,2,3,4-te-trahydropyrazino [1,2-a] indoles, Bioorg. Med. Chem. Lett. 16 (2006) 413-416; DOI: 10.1016/j. bmcl.2005.09.066.

E.R. El-Sawy, T.K. Mohamed and S.Y. El-Tablawy, Synthesis and in vitro antifungal activity of 3-[1,2,3-selena and thiadiazol-4-yl] indole and their fulvene derivatives, Egypt Pharm. J. (NRC). 5 (2006) 175-188.

S.J. Martin, J.E. O'Brien, J. Dowling, V.J. McBrierty and I. Krezel, New derivatives of imidazole as potential anticancer agents, Farmaco 53 (1998) 342-345; DOI: 10.1016/S0014-827X(98) 00031-7.

E. Szymanska and K. Kiec-Kononowicz, Antimicobacterial activity of 5-arylidene aromatic derivatives of hydantoin, Farmaco 57 (2002) 355-362; DOI: 10.1016/S0014-827X (01)01194-6.

W. Qinjie, W. Duoduo, G. Peng, F. Liang, H. Yongzhou, H. Qiaojun and Y. Bo, Q39, a novel synthetic quinoxaline 1,4-di-N-oxide compound with anticancer activity in hypoxia, Eur. J. Pharm. 581 (2008) 262; DOI: 10.1016/j.ejphar.2007.12.006.

S.A. Kotharkar and D.B. Shinde, Synthesis of antimicrobial 2,9,10-trisubstituted-6-oxo-7,12-di-hydro-chromeno[3,4-b] quinoxalines, Bioorg. Med. Chem. 14 (2006) 6181-6184; DOI: 10.1016/j. bmcl.2006.09.040.

A.L. Mndzhoyan, G.L. Papayan, L.D. Zhuruli, S.G. Karagezyan, L.S. Galstyan and V.G. Sarafyan, Synthesis and biological study of hydrazinohydrazones of indole aldehydes and ketones series, Arm. Khim. Zh. (USSR) 22 (1969) 707-713; ref. Chem. Abstr. 72 (1970) 11189f.

A.L. Barry and C. Thornsberry, Susceptibility Testing: Diffusion Test Procedures, in Manual of Clinical Microbiology (Eds. E.H. Lennette, A. Balows, W.J. Hausler Jr. and J.P. Truant), 3rd ed., American Society for Microbiology, Washington (DS) 1980, pp. 463-474.

T. Mosmann, Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays, J. Immunol. Meth. 65 (1983) 55-63; DOI: 10.1038/nbt089.716.

J.M. William, A.V. Edward, D.I. Dale and S. Youqing, Progesterone facilitates cisplatin toxicity in epithelial ovarian cancer cells and xenografts, Gynec. Oncol. 110 (2008) 251-255; DOI: 10.1016/j.ygyno.2008.03.021.

K. Bodendorf and A. Walk, Preparation and reaction of 3-indolyl aminomethyl ketons, Arch. Pharm. 294 (1961) 484-487.

J. Okuda, K. Inagaki, I. Miwa and K. Yashiro, Inhibition of aldose reductases from rat and bovine lenses by hydantoin derivatives, Chem. Pharm. Bull. 30 (1982) 3244-3254.

A.H. Mandour and E.M. Kassem, Synthesis of N-(coumarin sulfonyl) thiohydantoin and hydantoin derivatives, Afinidad. 489 (2000) 344-348.

J.S. Dickstein, M.W. Fennie, A.L. Norman, B.J. Paulose and M.C. Kozlowski, Three component coupling of alpha-iminoesters via umpolung addition of organometals: synthesis of alpha, alpha-disubstituted alpha-amino acids, J. Amer. Chem. Soc. 130 (2008) 15794-15795; DOI: 10.1021/ja8073006.

W. Reeve, R.S. Hudson and C.W. Woods, Synthesis of several methyl α-methoxy indole acetates related to the natural auxin, indole acetic acid, Tetrahedron 19 (1963) 1243-1249.

H. Bergstrand, K. Karabelas and P. Sjo, Preparation of Indolylbenzoquinoxalinones and Related Compounds as Protein Kinase C Inhibitors, PCT Int. Appl. WO 9813368 (1998); ref. Chem. Abstr. 128 (1998) 257445b.

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

Journal Information

IMPACT FACTOR 2017: 1.071
5-year IMPACT FACTOR: 1.623

CiteScore 2017: 1.46

SCImago Journal Rank (SJR) 2017: 0.362
Source Normalized Impact per Paper (SNIP) 2017: 0.642

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 218 218 20
PDF Downloads 85 85 5