Abstract
In this study, 5-chloro-1'-methyl-5'-nitro-3H-spiro[1,3-benzothiazole2,3'-indole]-2'(1'H)-one (3u) was synthesized by the reaction of 1-methyl5-nitro-1H-indole-2,3-dione (1m) with 2-amino-4-chlorothiophenol (2) in ethanol. The structure of 3u was confirmed by the spectral (IR, H NMR, HSQC-2D, LCMS-ESI) data and elemental analysis. The new spiroindolinone derivative 3u, along with previously reported spiroindolinone derivatives 3a-t bearing benzothiazole or 5-chlorobenzothiazole moiety were tested for in vitro antimicrobial activity against selected strains. Among the tested compounds, 3i and 3l displayed the highest efficacy against Staphylococcus aureus and Candida albicans. Only 3b was found to be significantly active against Staphylococcus epidermidis. 3a-n were evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis H37Rv, but most of the tested compounds showed weakly antitubercular activity. All compounds were also evaluated against some DNA and RNA viruses in CRFK, HeLa and HEL cells. Cytotoxicities of the tested compounds were generally very high compared to standards.*Correspondence: karalin@istanbul.edu.tr
Keywords
Spiroindolinones benzothiazole antimicrobial activity antituberculosis activity antiviral activity.
References
- 1. Da Silva, J.F.M., Garden, S.J., Pinto, A.C., The Chemistry of Isatins: a Review from 1975 to 1999, J. Braz. Chem. Soc. 12, 273-324 (2001).
- 2. Vine, K.L., Matesic, L., Locke, J.M., Ranson, M., Sklopeta, D., Cytotoxic and anticancer activity of isatin and its derivatives: a comprehensive review from 2000-2008, Anti-cancer Agents Med. Chem., 9, 397-414 (2009).
- 3. Singh, G.S., Desta, Z.Y., Isatin as privileged molecules in design and synthesis of spiro-fused cyclic frameworks, Chem. Rev., 112, 6104- 6155 (2012).
- 4. Bhaskar, G., Arun, Y., Balachandran, C., Saikumar, C., Perumal, P.T. Synthesis of novel spirooxindole derivatives by one pot multicomponent reaction and their antimicrobial activity, Eur. J. Med. Chem., 51, 79-91 (2012).
- 5. Karalı, N., Güzel, Ö., Özsoy, N., Özbey, S., Salman, A., Synthesis of new spiroindolinones incorporating a benzothiazole moiety as antioxidant agents. Eur. J. Med. Chem., 45, 1068-1077 (2010).
- 6. Akkurt, M., Karaca, S., Ermut, G., Karalı, N., Büyükgüngör, O., 5-Chlorobenzothiazole-2-spiro-3'-indolin-2’-one. Acta Cryst E66, o399-o400 (2010).
- 7. Görkem, E., Karalı N., Özsoy, N., Can, A., New spiroindolinones bearing 5-chlorobenzothiazole moiety, J. Enz. Inh. Med. Chem. (2013) (early online)
- 8. Naumov, P., Anastasova, F., Experimental and theoretical vibrational study of isatin, its 5-(NO2 , F, Cl, Br, I, CH3 ) analogues and the isatinato anion, Spectrochim. Acta Part A 57, 469-481 (2001).
- 9. Laatsch, H., Thomson, R.H., Cox, P.J., Spectroscopic properties of violacein and related compounds: crystal structure of tetramethylviolacein, J. Chem. Soc. Perkin Trans II 1331-1339 (1984).
- 10. Jayashankaran, J., Manian, R.D.R.S., Raghunathan, R., A facile synthesis of novel dispiroheterocycles through solvent-free microwaveassisted [3+2] cycloaddition of azomethine ylides, Tetrahedron Lett. 45, 7303-7305 (2004).
- 11. Wayne, PA. Clinical and Laboratory Standarts Institute:Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that grow Aerobically. Seventh Edition, Approved Standart M7-A7, CLSI, USA. 2006.
- 12. Clinical ans Laboratory Standards Institute (CLSI): Reference Method for Broth Dilution Antifungal Susceptbility Testing of Yeasts, Approved Standart M27-A2, Wayne. CLSI, USA. 2002.
- 13. Collins, L.A., Franzblau, S.G. Antimicrob. Agents Chemother., 41, 1004-1009 (1997).
- 14. Vanderlinden, E., Göktaş, F., Cesur, Z., Froeyen, M., Reed, M.L., Russel, C.J., Cesur, N., Naesens, L., Novel inhibitors of influenza virus fusion: Structure-activity relationship and interaction with the viral hemagglutinin. J. Virol., 84, 4277-4288 (2010)
Abstract
Bu çalışmada 1-metil-5-nitro-1H-indol-2,3-dion (1m) ile 2-amino-
4-klorotiyofenol (2)'ün etanollü ortamdaki reaksiyonundan 5-kloro-1'-
metil-5'-nitro-3H-spiro[1,3-benzotiyazol-2,3'-indol]-2'(1'H)-on
(3u) bileşiği sentezlenmiştir. 3u nun yapısı spektral (IR, 1
H NMR, HSQC-
2D, LCMS-ESI) bulgular ve elemental analiz ile kanıtlanmıştır. Yeni spiroindolinon
türevi 3u, daha önce rapor edilen benzotiyazol ya da 5-klorobenzotiyazol
artığı taşıyan spiroindolinon türevleri 3a-t ile birlikte seçilen
bakteri suşlarına karşı in vitro antibakteriyel aktivite için test edilmiştir.
Test edilen bileşikler içinde 3i ve 3l Staphylococcus aureus ve Candida
albicans'a karşı en yüksek etkinlik göstermiştir. Yalnız 3b Staphylococcus
epidermidis' e karşı önemli derecede etkili bulunmuştur. 3a-n nin
Mycobacterium tuberculosis H37Rv karşı in vitro antitüberküloz etkileri
incelenmiştir; ama test edilen bileşiklerin çoğu zayıf antitüberküloz etki
göstermiştir. Tüm bileşikler CRFK, HeLa ve HEL hücrelerinde DNA ve
RNA virüslerine karşı ayrıca test edilmiştir. Test edilen bileşiklerin sitotoksisiteleri
standartlara kıyasla genellikle çok yüksektir.
References
- 1. Da Silva, J.F.M., Garden, S.J., Pinto, A.C., The Chemistry of Isatins: a Review from 1975 to 1999, J. Braz. Chem. Soc. 12, 273-324 (2001).
- 2. Vine, K.L., Matesic, L., Locke, J.M., Ranson, M., Sklopeta, D., Cytotoxic and anticancer activity of isatin and its derivatives: a comprehensive review from 2000-2008, Anti-cancer Agents Med. Chem., 9, 397-414 (2009).
- 3. Singh, G.S., Desta, Z.Y., Isatin as privileged molecules in design and synthesis of spiro-fused cyclic frameworks, Chem. Rev., 112, 6104- 6155 (2012).
- 4. Bhaskar, G., Arun, Y., Balachandran, C., Saikumar, C., Perumal, P.T. Synthesis of novel spirooxindole derivatives by one pot multicomponent reaction and their antimicrobial activity, Eur. J. Med. Chem., 51, 79-91 (2012).
- 5. Karalı, N., Güzel, Ö., Özsoy, N., Özbey, S., Salman, A., Synthesis of new spiroindolinones incorporating a benzothiazole moiety as antioxidant agents. Eur. J. Med. Chem., 45, 1068-1077 (2010).
- 6. Akkurt, M., Karaca, S., Ermut, G., Karalı, N., Büyükgüngör, O., 5-Chlorobenzothiazole-2-spiro-3'-indolin-2’-one. Acta Cryst E66, o399-o400 (2010).
- 7. Görkem, E., Karalı N., Özsoy, N., Can, A., New spiroindolinones bearing 5-chlorobenzothiazole moiety, J. Enz. Inh. Med. Chem. (2013) (early online)
- 8. Naumov, P., Anastasova, F., Experimental and theoretical vibrational study of isatin, its 5-(NO2 , F, Cl, Br, I, CH3 ) analogues and the isatinato anion, Spectrochim. Acta Part A 57, 469-481 (2001).
- 9. Laatsch, H., Thomson, R.H., Cox, P.J., Spectroscopic properties of violacein and related compounds: crystal structure of tetramethylviolacein, J. Chem. Soc. Perkin Trans II 1331-1339 (1984).
- 10. Jayashankaran, J., Manian, R.D.R.S., Raghunathan, R., A facile synthesis of novel dispiroheterocycles through solvent-free microwaveassisted [3+2] cycloaddition of azomethine ylides, Tetrahedron Lett. 45, 7303-7305 (2004).
- 11. Wayne, PA. Clinical and Laboratory Standarts Institute:Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that grow Aerobically. Seventh Edition, Approved Standart M7-A7, CLSI, USA. 2006.
- 12. Clinical ans Laboratory Standards Institute (CLSI): Reference Method for Broth Dilution Antifungal Susceptbility Testing of Yeasts, Approved Standart M27-A2, Wayne. CLSI, USA. 2002.
- 13. Collins, L.A., Franzblau, S.G. Antimicrob. Agents Chemother., 41, 1004-1009 (1997).
- 14. Vanderlinden, E., Göktaş, F., Cesur, Z., Froeyen, M., Reed, M.L., Russel, C.J., Cesur, N., Naesens, L., Novel inhibitors of influenza virus fusion: Structure-activity relationship and interaction with the viral hemagglutinin. J. Virol., 84, 4277-4288 (2010)
Details
| Primary Language | English |
|---|---|
| Subjects | Pharmacology and Pharmaceutical Sciences |
| Journal Section | Makaleler |
| Authors | |
| Publication Date | March 24, 2014 |
| Published in Issue | Year 2013 Volume: 43 Issue: 1 |
