A small library of 2-[(1H-indol-3-yl)methyl]-5-(alkylthio)-1,3,4-oxadiazoles was prepared, starting from indole-3-acetic acid methyl ester and its 5-methyl-substituted derivative. The synthetic route involved the formation of intermediate hydrazides, their condensation with carbon disulfide, and intramolecular cyclization to corresponding 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones. The latter were then S-alkylated, and in case of ester derivatives, they were further hydrolyzed into corresponding carboxylic acids. All 5-[(1H-indol-3-yl)methyl]-1,3,4-oxadiazole-2(3H)-thiones and their S-alkylated derivatives were then screened for their protective effects in vitro and in vivo. Methyl substitution on the indole ring and propyl, butyl, or benzyl substitution on sulfhydryl group-possessing compounds were revealed to protect Friedreich's ataxia fibroblasts against the effects of glutathione depletion induced by the γ-glutamylcysteine synthetase inhibitor, buthionine sulfoximine. Two of the active compounds also reproducibly increased the survival of Caenorhabditis elegans exposed to juglone-induced oxidative stress.

Department of Chemical Biology Faculty of Science Palacký University Olomouc Czech Republic

Department of Clinical and Molecular Pathology Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacký University Olomouc Czech Republic

Department of Experimental Biology Faculty of Science Palacký University Olomouc Czech Republic

Department of Microbiology Faculty of Medicine and Dentistry Palacký University Olomouc Czech Republic

Department of Organic Chemistry Kaunas University of Technology Kaunas Lithuania

Laboratory of Growth Regulators Institute of Experimental Botany of the Czech Academy of Sciences and Faculty of Science Palacký University Olomouc Czech Republic

Zobrazit více v PubMed

J. Boström, A. Hogner, A. Llinàs, E. Wellner, A. T. Plowright, J. Med. Chem. 2012, 55, 1817.

G. Verma, M. F. Khan, W. Akhtar, M. M. Alam, M. Akhter, M. Shaquiquzzaman, Mini Rev. Med. Chem. 2019, 19, 477.

P. Pitasse-Santos, V. Sueth-Santiago, M. Lima, J. Braz. Chem. Soc. 2018, 29, 435.

E. Yarmohammadi, H. Beyzaei, R. Aryan, A. Moradi, Mol. Divers. 2020. https://doi.org/10.1007/s11030-020-10125-y

N. Mihailović, V. Marković, I. Z. Matić, N. S. Stanisavljević, Ž. S. Jovanović, S. Trifunović, L. Joksović, RSC Adv. 2017, 7, 8550.

R. Shakir, A. Ariffin, M. Abdulla, Molecules 2014, 19, 3436.

Y. Kotaiah, N. Harikrishna, K. Nagaraju, C. Venkata Rao, Eur. J. Med. Chem. 2012, 58, 340.

K. N. Mohana, C. B. P. Kumar, ISRN Org. Chem. 2013, 2013, 1.

S. Nazar, N. Siddiqui, O. Alam, Arch. Pharm. (Weinheim) 2020, 353, 1900342.

D. Kumar, V. Kumar, R. Marwaha, G. Singh, Curr. Bioact. Compd. 2019, 15, 271.

T. Glomb, K. Szymankiewicz, P. Świątek, Molecules 2018, 23, 3361.

I. Khan, A. Ibrar, N. Abbas, Arch. Pharm. (Weinheim) 2014, 347, 1.

T. Ozyazici, E. E. Gurdal, D. Orak, H. Sipahi, T. Ercetin, H. O. Gulcan, M. Koksal, Arch. Pharm. (Weinheim) 2020, 353, 2000061.

G. Chawla, B. Naaz, A. A. Siddiqui, Mini Rev. Med. Chem. 2018, 18, 216. https://doi.org/10.2174/1389557517666170127121215

S. S. De, M. P. Khambete, M. S. Degani, Bioorg. Med. Chem. Lett. 2019, 29, 1999.

H. Kashtoh, S. Hussain, A. Khan, S. M. Saad, J. A. J. Khan, K. M. Khan, S. Perveen, M. I. Choudhary, Bioorg. Med. Chem. 2014, 22, 5454.

M. Iftikhar, Shahnawaz, M. Saleem, N. Riaz, Aziz-ur-Rehman, I. Ahmed, J. Rahman, M. Ashraf, M. S. Sharif, S. U. Khan, T. T. Htar, Arch. Pharm. (Weinheim) 2019, 352, 1900095.

C. R. W. Guimarães, D. L. Boger, W. L. Jorgensen, J. Am. Chem. Soc. 2005, 127(49), 17377. https://doi.org/10.1021/JA055438J

J. H. Lee, T. K. Wood, J. Lee, Trends Microbiol. 2015, 23, 707.

E. Hényková, H. P. Vránová, P. Amakorová, T. Pospíšil, A. Žukauskaite, M. Vlčková, L. Urbánek, O. Novák, J. Mareš, P. Kaňovský, M. Strnad, J. Chromatogr. A 2016, 1437, 145. https://doi.org/10.1016/j.chroma.2016.02.009

A. Pěnčík, R. Casanova-Sáez, V. Pilařová, A. Žukauskaitė, R. Pinto, J. L. Micol, K. Ljung, O. Novák, J. Exp. Bot. 2018, 69, 2569.

M. Kanlayavattanakul, N. Lourith, J. Cosmet. Sci. 2015, 66, 371.

A. J. Kochanowska-Karamyan, M. T. Hamann, Chem. Rev. 2010, 110, 4489.

N. Netz, T. Opatz, Mar. Drugs 2015, 13, 4814.

M. S. Estevão, L. C. Carvalho, D. Ribeiro, D. Couto, M. Freitas, A. Gomes, L. M. Ferreira, E. Fernandes, M. M. B. Marques, Eur. J. Med. Chem. 2010, 45, 4869.

T. Herraiz, J. Galisteo, Free Radic. Res. 2004, 38, 323.

J. Kumar, N. Kumar, N. Sati, P. K. Hota, New J. Chem. 2020, 44, 8960.

S. Suzen, S. S. Cihaner, T. Coban, Chem. Biol. Drug Des. 2012, 79, 76.

Y. Wan, Y. Li, C. Yan, M. Yan, Z. Tang, Eur. J. Med. Chem. 2019, 183, 111691. https://doi.org/10.1016/j.ejmech.2019.111691

S. Dadashpour, S. Emami, Eur. J. Med. Chem. 2018, 150, 9.

D. Kumar, N. M. Kumar, B. Noel, K. Shah, Eur. J. Med. Chem. 2012, 55, 432.

K. Nguyen, A. Khachemoune, J. Dermatol. Treat. 2019, 30, 732.

J. Atchison, S. Kamila, H. Nesbitt, K. A. Logan, D. M. Nicholas, C. Fowley, J. Davis, B. Callan, A. P. McHale, J. F. Callan, Chem. Commun. 2017, 53, 2009.

G. Varvuolytė, L. Malina, A. Bieliauskas, B. Hošíková, H. Simerská, H. Kolářová, N. Kleizienė, V. Kryštof, A. Šačkus, A. Žukauskaitė, Dyes Pigments 2020, 183, 108666.

J. Mendoza-Avila, K. Chauhan, R. Vazquez-Duhalt, Dyes Pigments 2020, 178, 108384.

Y. Wang, Z. Wan, C. Jia, X. Yao, Synth. Met. 2016, 211, 40.

M. Dagilienė, V. Martynaitis, V. Kriščiūnienė, S. Krikštolaitytė, A. Šačkus, ChemistryOpen 2015, 4, 363.

G. Ragaite, M. Dagiliene, S. Krikštolaityte, V. Martynaitis, A. Šačkus, J. Fluor. Chem. 2016, 182, 34.

Y. Lv, Y. Guo, J. Xu, S. Shao, J. Fluor. Chem. 2011, 132, 973.

M. You, H. Fan, Y. Wang, W. Zhang, Chem. Phys. 2019, 526, 110438.

W. Luo, M. Lei, Y. Wang, H. Gao, Y. Wang, Q. Zhou, Z. Xu, F. Yang, Anal. Methods 2019, 11, 1080.

Y. Rong, C. Wang, P. Chuai, Y. Song, S. Zhou, P. Hou, X. Liu, L. Wei, X. Song, New J. Chem. 2019, 43, 13212.

M.-Z. Zhang, N. Mulholland, D. Beattie, D. Irwin, Y.-C. Gu, Q. Chen, G.-F. Yang, J. Clough, Eur. J. Med. Chem. 2013, 63, 22.

N. Siddiqui, M. S. Alam, W. Ahsan, Acta Pharm. 2008, 58, 445.

Z. L. Song, Y. Zhu, J. R. Liu, S. K. Guo, Y. C. Gu, X. Han, H. Q. Dong, Q. Sun, W. H. Zhang, M. Z. Zhang, Mol. Divers. 2020, 1, 3.

K. Rubab, M. A. Abbasi, A. ur-Rehman, S. Z. Siddiqui, M. Ashraf, A. Shaukat, I. Ahmad, M. A. Lodhi, F. A. Khan, M. Shahid, M. N. Akhtar, Brazilian J. Pharm. Sci. 2015, 51, 931.

M. A. Z. Abu-Zaied, G. A. M. Nawwar, R. H. Swellem, S. H. El-Sayed, M. A. Z. Abu-Zaied, G. A. M. Nawwar, R. H. Swellem, S. H. El-Sayed, Pharmacol. Pharm. 2012, 03, 254.

X.-S. Ning, M.-M. Wang, J.-P. Qu, Y.-B. Kang, J. Org. Chem. 2018, 83, 13523.

L. L. Remsing Rix, B. M. Kuenzi, Y. Luo, E. Remily-Wood, F. Kinose, G. Wright, J. Li, J. M. Koomen, E. B. Haura, H. R. Lawrence, U. Rix, ACS Chem. Biol. 2014, 9, 353.

A. K. Singh, V. Raj, S. Saha, Eur. J. Med. Chem. 2017, 142, 244.

K. Bieleszová, B. Pařízková, M. Kubeš, A. Husičková, M. Kubala, Q. Ma, M. Sedlářová, S. Robert, K. Doležal, M. Strnad, O. Novák, A. Žukauskaitė, N. Biotechnol. 2019, 48, 44.

K. Rubab, M. A. Abbasi, A. Rehman, S. Z. Siddiqui, S. A. A. Shah, M. Ashraf, Q. Ain, I. Ahmad, M. A. Lodhi, M. Ghufran, M. Shahid, H. Fatima, Pak. J. Pharm. Sci. 2017, 30, 1263.

M. A. Z. Abu-Zaied, G. A. M. Nawwar, R. H. Swellem, S. H. El-Sayed, Pharmacol. Pharm. 2012, 03, 254.

R. Abu Khalaf, A. M. Abdula, M. S. Mubarak, M. O. Taha, Med. Chem. Res. 2015, 24, 2529.

H. Gadegoni, S. Manda, Chinese Chem. Lett. 2013, 24, 127.

B. Uttara, A. Singh, P. Zamboni, R. Mahajan, Curr. Neuropharmacol. 2009, 7, 65.

P. Davalli, T. Mitic, A. Caporali, A. Lauriola, D. D'Arca, Oxid. Med. Cell Longev. 2016, 2016, 3565127. https://doi.org/10.1155/2016/3565127

I. Liguori, G. Russo, F. Curcio, G. Bulli, L. Aran, D. Della-Morte, G. Gargiulo, G. Testa, F. Cacciatore, D. Bonaduce, P. Abete, Clin. Interv. Aging. 2018, 13, 757.

R. E. Smith, T. Ozben, L. Saso, Oxid. Med. Cell Longev. 2019, 2019, 6380473. https://doi.org/10.1155/2019/6380473

G. Pizzino, N. Irrera, M. Cucinotta, G. Pallio, F. Mannino, V. Arcoraci, F. Squadrito, D. Altavilla, A. Bitto, Oxid. Med. Cell Longev. 2017, 2017, 8416763. https://doi.org/10.1155/2017/8416763

M. Bingul, M. F. Saglam, H. Kandemir, M. Boga, I. F. Sengul, Monatsh. Chem. 2019, 150, 1553.

J. L. Bradley, S. Homayoun, P. E. Hart, A. H. V. Schapira, J. M. Cooper, Neurochem. Res. 2004, 29, 561.

A. K. Corsi, B. Wightman, M. Chalfie, WormBook 2015, 1.

V. Milišiūnaitė, A. Kadlecová, A. Žukauskaitė, K. Doležal, M. Strnad, J. Voller, E. Arbačiauskienė, W. Holzer, A. Šačkus, Mol. Divers. 2020, 24, 1025.

N. T. M. Markaki, Curr. Opin. Biotechnol. 2020, 63, 118.

L. P. O'Reilly, C. J. Luke, D. H. Perlmutter, G. A. Silverman, S. C. Pak, Adv. Drug Deliv. Rev. 2014, 69-70, 247.

E. Culetto, D. B. Sattelle, Hum. Mol. Genet. 2000, 9, 869. https://doi.org/10.1093/hmg/9.6.869

A. Kadlecová, T. Jirsa, O. Novák, J. Kammenga, M. Strnad, J. Voller, Biogerontology 2018, 19, 109. https://doi.org/10.1007/s10522-017-9742-4

V. H. C. Liao, C. W. Yu, Y. J. Chu, W. H. Li, Y. C. Hsieh, T. T. Wang, Mech. Ageing Dev. 2011, 132, 480. https://doi.org/10.1016/j.mad.2011.07.008

C. W. Yu, C. C. Wei, V. H. C. Liao, Free Radic. Res. 2014, 48, 371. https://doi.org/10.3109/10715762.2013.872779

M. P. Mattson, Ageing Res. Rev. 2008, 7, 1.

K. Bürk, Cerebellum Ataxias 2017, 4, 4. https://doi.org/10.1186/s40673-017-0062-x

T. E. Richardson, A. E. Yu, Y. Wen, S.-H. Yang, J. W. Simpkins, PLOS One 2012, 7, e34600.

T. E. Richardson, J. W. Simpkins, BMC Pharmacol. Toxicol. 2012, 13, 12.

K. Präbst, H. Engelhardt, S. Ringgeler, H. Hübner, Methods Mol. Biol. 2017, 1601, 1.

S. Brenner, Genetics 1974, 77, 71.

R. Stiernagle, WormBook 2006. https://doi.org/10.1895/wormbook.1.101.1