Mіnі-rеvіеw: Advаnсеs іn thе sуnthеsіs аnd bіоlоgісаl асtіvіtу оf bеnzоfurохаn аnd furохаn dеrіvаtіvеs
Keywords:
bеnzоfurохаn, furохаn, NО dоnоr, hеtеrосусlіс соmроunds, hуbrіd соmроunds, аntіbасtеrіаl рrореrtіеs, аntіvіrаl аnd аntіtumоr drugs
Abstract
Benzofuroxan and furoxan derivatives are heterocyclic compounds well known for their ability to act as nitric oxide (NO) donors. Due to their NO-releasing properties, these compounds have attracted considerable attention for their antimicrobial, antiviral, and antitumor activities. Their potential use in treating cardiovascular, gastrointestinal, and neurodegenerative disorders further underscores their pharmacological relevance. Given the increasing research interest in these compounds, there is a need to consolidate recent findings related to their chemical properties and biological potential. This mini-review aims to provide an up-to-date overview of the synthetic strategies and bioactivities of benzofuroxan and furoxan derivatives. Rather than focusing on ring synthesis, this review highlights the reactivity of side-chain functional groups and the design of hybrid molecules. Representative examples of drug-like compounds are discussed, along with their biological profiles. The review also explores emerging directions in the development of novel NO donors based on these frameworks with improved pharmaceutical efficacy and controlled NO release.
References
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38 Ustyuzhanina NE, Fershtat LL, Gening ML, Nifantiev NE, Makhova NN (2016) Mendeleev Commun 26:513–515. Crossref
39 Orlandi VT, Bolognese F, Rolando B, Guglielmo S, Lazzarato L, Fruttero R (2018) Microbiology 164:1557–1566. Crossref
40 Fei Y, Wu J, An H-W, Zhu K, Peng B, Cai J, et al. (2020) J Med Chem 63:9127–9135. Crossref
41 Huang LY, Tsui DY, Williams CM, Wyse BD, Smith MT (2015) Clin Exp Pharmacol Physiol 42:921–929. Crossref
42 Makhova NN, Fershtat LL (2018) Tetrahedron Lett 59:2317–2326. Crossref
43 Pippin AB, Mohd Arshad ZH, Voll RJ, Nye JA, Ghassabian S, Williams CM, et al. (2016) ACS Med Chem Lett 7:563–567. Crossref
44 Huang L, Wyse BD, Williams CM, Smith MT (2019) Clin Exp Pharmacol Physiol 46:676–685. Crossref
45 Schiefer IT, VandeVrede L, Fa’ M, Arancio O, Thatcher GRJ (2012) J Med Chem 55:3076–3087. Crossref
46 de Carvalho PS, Maróstica M, Gambero A, Pedrazzoli J (2010) Eur J Med Chem 45:2489–2493. Crossref
47 Chugunova E, Matveeva V, Tulesinova A, Iskanderov E, Akylbekov N, Dobrynin A, et al. (2022)Int J Mol Sci. Crossref
48 Chugunova EA, Burilov AR (2017) Curr Top Med Chem 17:986–1005. Crossref
49 dos Santos Fernandes GF, de Souza PC, Marino LB, Chegaev K, Guglielmo S, Lazzarato L, et al. (2016) Eur J Med Chem 123:523–531. Crossref
50 Zhang Z, Bai Z-W, Ling Y, He L-Q, Huang P, Gu H-X, et al. (2018) Med Chem Res 27:1198–1205. Crossref
51 Abdelall EKA (2020) Bioorg Chem 94:103441. Crossref
52 Fershtat L, Bystrov D, Zhilin E, Makhova N (2019) Synthesis (Stuttg) 51:747–756. Crossref
53 Chugunova E, Gibadullina E, Matylitsky K, Bazarbayev B, Neganova M, Volcho K, et al. (2023) Pharmaceuticals 16:499. Crossref
54 Sotgia F, Martinez-Outschoorn UE, Lisanti MP (2011) BMC Med 9:62. Crossref
55 Smolobochkin A, Gazizov A, Sazykina M, Akylbekov N, Chugunova E, Sazykin I, et al. (2019) Molecules 24:3086. Crossref
56 Chugunova E, Matveeva V, Tulesinova A, Iskanderov E, Akylbekov N, Dobrynin A, et al. (2022) Int J Mol Sci 23:14902. Crossref
57 Khan FH, Dervan E, Bhattacharyya DD, McAuliffe JD, Miranda KM, Glynn SA (2020) Int J Mol Sci 21:9393. Crossref
58 Shpakovsky DB, Banti CN, Mukhatova EM, Gracheva YA, Osipova VP, Berberova NT, et al. (2014) Dalt Trans 43:6880–6890. Crossref
59 Wang L, Li C, Zhang Y, Qiao C (2013) J Agric Food Chem 61:8632−8640. Crossref
60 Bogdanov AV, Iskhakova KR, Voloshina AD, Sapunova AS, Kulik NV, Terekhova NV, et al. (2020) Chem Biodivers 17: e2000147. Crossref
61 de Giacometi M, Mayer JCP, de Mello AB, Islabão YW, Strothmann AL, da Fonseca RN, et al. (2023) Exp Parasitol 253:108601. Crossref
62 Gala UH, Miller DA, Williams RO (2020) Biochim Biophys Acta - Rev Cancer 1873:188319. Crossref
63 DIMITRIOS B (2006) Trends Food Sci Technol 17:505–512. Crossref
64 Truong DH, Tran TH, Ramasamy T, Choi JY, Choi H-G, Yong CS, et al. (2015) Powder Technol 283:260–265. Crossref
65 Boudou-Rouquette P, Ropert S, Mir O, Coriat R, Billemont B, Tod M, et al. (2012) Oncologist 17:1204–1212. Crossref
66 Boudou-Rouquette P, Narjoz C, Golmard JL, Thomas-Schoemann A, Mir O, Taieb F, et al. (2012) PLoS One 7:1–9. Crossref
67 Zhanakov MN, Matveeva VI, Akylbekov NI, Chugunova EA, Khamatgalimov AR, Burilov AR, et al. (2023) Russ J Gen Chem 93:S491–S500. Crossref
2 Gasco A, Boulton AJ (1981)In: Katritzky AR, Boulton AJ (eds) Furoxans and Benzofuroxans, Adv. Heterocycl. Chem. Academic Press, London, pp 251–340. Crossref
3 N.B.Grigoriev VGG (2004) Oxid Azota (NO): Novyi put’ k Poisku Lekarstv [Nitric Oxide (NO): New Approach to Drug Search]. University Book, Moscow.
4 Fershtat LL, Makhova NN (2017) ChemMedChem 12:622–638. Crossref
5 Gasco A, Fruttero R, Sorba G, Di Stilo A, Calvino R (2004) Pure Appl Chem 76:973–981. Crossref
6 Cerecetto H, González M (2007) Benzofuroxan and Furoxan. Chemistry and Biology. pp 265–308. Crossref
7 Medana C, Di Stilo A, Visentin S, Fruttero R, Gasco A, Ghigo D, et al. (1999) Pharm Res 16:956–60. Crossref
8 Abu Yousef M, Matsubara R (2023) RSC Adv 13:5228–5248. Crossref
9 Mallory FB, Cammarata A (1966) J Am Chem Soc 88:61–64. Crossref
10 Ferioli R, Folco GC, Ferretti C, Gasco AM, Medana C, Fruttero R, et al. (1995) Br J Pharmacol 114:816–820. Crossref
11 R.Calvino, V.Mortarini, A.Gasco MAB and MLR (1977) Synth Antimicrob Act 12:157–159.
12 Cerecetto H, Porcal W (2005) Mini-Reviews Med Chem 5:57–71. Crossref
13 J.Stevens, M. Schweizer GR (2001)Some recent studies on benzofuraxansJournal of the American Chemical Society 123:
14 Flores-Santana W, Salmon DJ, Donzelli S, Switzer CH, Basudhar D, Ridnour L, et al. (2011) Antioxid Redox Signal 14:1659–1674. Crossref
15 Zavarzina O V., Rakitin OA, Khmel’nitskii LI (1994) Mendeleev Commun 4:135. Crossref
16 Sebban M, Goumont R, Hallé JC, Terrier F, Marrot J (1999) Chem Commun 1009–1010. Crossref
17 Y.Fukai, T.Miyazawa, M.Kojoh, T.Takabatake MH (2001) JHeterocyclChem 38:531–534.
18 David M. Jameson and Shan S. Wong (2011) Chemistry of Protein and Nucleic Acid Cross-Linking and Conjugation.
19 Kumar S, Arora A, Chaudhary R, Kumar R, Len C, Mukherjee M, et al. (2024) Top Curr Chem 382:34. Crossref
20 Bohn H, Brendel J, Martorana PA, Schönafinger K (1995) Br J Pharmacol 114:1605–1612. Crossref
21 Ustyuzhanina NE, Fershtat LL, Gening ML, Nifantiev NE, Makhova NN (2018) Mendeleev Commun 28:49–51. Crossref
22 Civelli M, Giossi M, Caruso P, Razzetti R, Bergamaschi M, Bongrani S, et al. (1996) Br J Pharmacol 118:923–928. Crossref
23 Wang PG, Bill Cai T, Taniguchi N (2005) Nitric Oxide Donors. Wiley. Crossref
24 Fershtat LL, Makhova NN (2017) ChemMedChem 12:622–638. Crossref
25 Burov ON, Kletskii ME, Fedik NS, Lisovin A V, Kurbatov S V (2015) Chem Heterocycl Compd 51:951–960. Crossref
26 Chugunova EAA, Gazizov ASS, Burilov ARR, Yusupova LMM, Pudovik MAA, Sinyashin OGG (2019) Russ Chem Bull 68:887–910. Crossref
27 Zhilin ES, Fershtat LL, Bystrov DM, Kulikov AS, Dmitrienko AO, Ananyev I V., et al. (2019) European J Org Chem 2019:4248–4259. Crossref
28 Zhilin ES, Polkovnichenko MS, Ananyev I V., Fershtat LL, Makhova NN (2020) ChemPhotoChem 4:5346–5354. Crossref
29 Garipov MR, Nikitina EV, Petukhov AS, Shtyrlin YuG, Strelnik AD (2013) Antibacterial compounds based on sulfanilic acid and pyridoxine [Antibakterial’nye soedineniya na osnove sul’fanilovoy kisloty i piridoksina]. Patent of the Russian Federation RF Patent 2480471, Int. Cl. C07D491/052. Published 27.04.2013. (In Russian)
30 Serkov IV, Bezuglov VV (2009) Uspekhi Khimii [Russian Chemical Reviews] 78:442–465. (In Russian)
31 Katritzky AR, Gordeev MF (1993) Heterocycles 35:483–518. Crossref
32 Ghosh P, Ternai B, Whitehouse M (1981) Med Res Rev 1:159–187. Crossref
33 Fernandes GFS, Campos DL, Da Silva IC, Prates JLB, Pavan AR, Pavan FR, et al. (2021) ChemMedChem 16:1268–1282. Crossref
34 Fedik NS, Kletskii ME, Burov ON, Lisovin AV, Kurbatov SV, Chistyakov VA, et al. (2019) Nitric Oxide 93:15–24. Crossref
35 Chugunova E, Frenna V, Consiglio G, Micheletti G, Boga C, Akylbekov N, et al. (2020) J Org Chem 85:13472–13480. Crossref
36 Sema L Ioffe (2007) “Nitronates”, Nitrile Oxides Nitrones and Nitronates in Organic Synthesis. Ed. by Henry Feuer. A John Wiley & Sons, Inc., Publication, Canada.
37 Chugunova E, Micheletti G, Telese D, Boga C, Islamov D, Usachev K, et al. (2021) Int J Mol Sci 22:7497. Crossref
38 Ustyuzhanina NE, Fershtat LL, Gening ML, Nifantiev NE, Makhova NN (2016) Mendeleev Commun 26:513–515. Crossref
39 Orlandi VT, Bolognese F, Rolando B, Guglielmo S, Lazzarato L, Fruttero R (2018) Microbiology 164:1557–1566. Crossref
40 Fei Y, Wu J, An H-W, Zhu K, Peng B, Cai J, et al. (2020) J Med Chem 63:9127–9135. Crossref
41 Huang LY, Tsui DY, Williams CM, Wyse BD, Smith MT (2015) Clin Exp Pharmacol Physiol 42:921–929. Crossref
42 Makhova NN, Fershtat LL (2018) Tetrahedron Lett 59:2317–2326. Crossref
43 Pippin AB, Mohd Arshad ZH, Voll RJ, Nye JA, Ghassabian S, Williams CM, et al. (2016) ACS Med Chem Lett 7:563–567. Crossref
44 Huang L, Wyse BD, Williams CM, Smith MT (2019) Clin Exp Pharmacol Physiol 46:676–685. Crossref
45 Schiefer IT, VandeVrede L, Fa’ M, Arancio O, Thatcher GRJ (2012) J Med Chem 55:3076–3087. Crossref
46 de Carvalho PS, Maróstica M, Gambero A, Pedrazzoli J (2010) Eur J Med Chem 45:2489–2493. Crossref
47 Chugunova E, Matveeva V, Tulesinova A, Iskanderov E, Akylbekov N, Dobrynin A, et al. (2022)Int J Mol Sci. Crossref
48 Chugunova EA, Burilov AR (2017) Curr Top Med Chem 17:986–1005. Crossref
49 dos Santos Fernandes GF, de Souza PC, Marino LB, Chegaev K, Guglielmo S, Lazzarato L, et al. (2016) Eur J Med Chem 123:523–531. Crossref
50 Zhang Z, Bai Z-W, Ling Y, He L-Q, Huang P, Gu H-X, et al. (2018) Med Chem Res 27:1198–1205. Crossref
51 Abdelall EKA (2020) Bioorg Chem 94:103441. Crossref
52 Fershtat L, Bystrov D, Zhilin E, Makhova N (2019) Synthesis (Stuttg) 51:747–756. Crossref
53 Chugunova E, Gibadullina E, Matylitsky K, Bazarbayev B, Neganova M, Volcho K, et al. (2023) Pharmaceuticals 16:499. Crossref
54 Sotgia F, Martinez-Outschoorn UE, Lisanti MP (2011) BMC Med 9:62. Crossref
55 Smolobochkin A, Gazizov A, Sazykina M, Akylbekov N, Chugunova E, Sazykin I, et al. (2019) Molecules 24:3086. Crossref
56 Chugunova E, Matveeva V, Tulesinova A, Iskanderov E, Akylbekov N, Dobrynin A, et al. (2022) Int J Mol Sci 23:14902. Crossref
57 Khan FH, Dervan E, Bhattacharyya DD, McAuliffe JD, Miranda KM, Glynn SA (2020) Int J Mol Sci 21:9393. Crossref
58 Shpakovsky DB, Banti CN, Mukhatova EM, Gracheva YA, Osipova VP, Berberova NT, et al. (2014) Dalt Trans 43:6880–6890. Crossref
59 Wang L, Li C, Zhang Y, Qiao C (2013) J Agric Food Chem 61:8632−8640. Crossref
60 Bogdanov AV, Iskhakova KR, Voloshina AD, Sapunova AS, Kulik NV, Terekhova NV, et al. (2020) Chem Biodivers 17: e2000147. Crossref
61 de Giacometi M, Mayer JCP, de Mello AB, Islabão YW, Strothmann AL, da Fonseca RN, et al. (2023) Exp Parasitol 253:108601. Crossref
62 Gala UH, Miller DA, Williams RO (2020) Biochim Biophys Acta - Rev Cancer 1873:188319. Crossref
63 DIMITRIOS B (2006) Trends Food Sci Technol 17:505–512. Crossref
64 Truong DH, Tran TH, Ramasamy T, Choi JY, Choi H-G, Yong CS, et al. (2015) Powder Technol 283:260–265. Crossref
65 Boudou-Rouquette P, Ropert S, Mir O, Coriat R, Billemont B, Tod M, et al. (2012) Oncologist 17:1204–1212. Crossref
66 Boudou-Rouquette P, Narjoz C, Golmard JL, Thomas-Schoemann A, Mir O, Taieb F, et al. (2012) PLoS One 7:1–9. Crossref
67 Zhanakov MN, Matveeva VI, Akylbekov NI, Chugunova EA, Khamatgalimov AR, Burilov AR, et al. (2023) Russ J Gen Chem 93:S491–S500. Crossref
Published
2025-03-31
How to Cite
ZhаnаkоvM., Zhatkanbayeva, Z., СhugunоvаE., Akylbekov, N., & ZhаtkаnbауеvY. (2025). Mіnі-rеvіеw: Advаnсеs іn thе sуnthеsіs аnd bіоlоgісаl асtіvіtу оf bеnzоfurохаn аnd furохаn dеrіvаtіvеs. Chemical Bulletin of Kazakh National University, 114(1), 22-37. https://doi.org/https://doi.org/10.15328/cb1391
Section
Organic and Polymers Chemistry
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