MESOIONIC SYDNONE: A REVIEW IN THEIR CHEMICAL AND BIOLOGICAL PROPERTIES


Abdualrahman Mohammed Abdualkader, Muhammad Taher, Nik Idris Nik Yusoff

Abstract


Various literature sources have documented sydnones as important molecules with exclusive chemical properties and a wide spectrum of bioactivities. Sydnone can be defined as a five-membered pseudo-aromatic heterocyclic molecule. Classically, 1,2,3-oxadiazole forms the main skeleton of sydnone. The molecule has delocalized balanced positive and negative charges. The five annular atoms share the positive charge and the enolate-like exocyclic oxygen atom bears the negative charge. The hydrogen atom at the position C4 was proved to have acidic and nucleophilic functionalities making the sydnone ring reactive towards electrophilic reagents. These unique chemical features enable sydnones to interact with biomolecules resulting in important therapeutic effects like anticancer, antidiabetic, antimicrobial, antioxidant and anti-inflammatory. Consequently, we aim from the current article to review the available chemical and pharmacological information on sydnone and its derivatives.


Keywords


Sydnone, Mesoionic, Heterocycles, Anticancer, Antimicrobial, Anti-inflammatory

| PDF | HTML |

References


Baker W, Ollis WD. Mesoionic compounds. Quart Rev Chem Soc 1957;11:15-29.

Browne DL, Harrity JP. Recent developments in the chemistry of sydnones. Tetrahedron 2010;66:553-68.

Azarifar D, Bosra HG, Tajbaksh M. 1,3-Dibromo-5,5-dimethylhydantoin (DBH) as an efficient promoter for acetylation of 3-arylsydnones in the presence of acetic anhydride under neutral conditions. J Heterocycl Chem 2007;44:467-9.

Ueng CH, Wang Y, Yeh MY. Structures of 4-acetyl-3-(p-tolyl)sydnone and 4-acetyl-3-phenylsydnone oxime. Acta Crystallogr Sect C: Struct Chem 1987;43:1122-5.

Earl JC, Mackney AW. The action of acetic anhydride on N-nitrosophenylglycine and some of its derivatives. J Chem Soc (Resumed); 1935. p. 899-900.

Baker W, Ollis WD, Poole VD. Cyclic mesoionic compounds. Part III. Further properties of the sydnones and the mechanism of their formation. J Chem Soc (Resumed); 1950. p. 1542-51.

Chandrasekhar R, Nanjan MJ. Sydnones: a brief review. Mini Rev Med Chem 2012;12:1359-65.

Baker W, Ollis WD. Structure of the sydnones. Nature 1946;16:703.

Eade RA, Earl JC. The sydnones. a new class of compound containing two adjacent nitrogen atoms. J Chem Soc (Resumed); 1946. p. 591-93.

Kenner J, Mackay K. Structure of the sydnones. Nature 1946;21:909-10.

Applegate J, Turnbull K. The efficient synthesis of 3-arylsydnones under neutral conditions. Synthesis 1988;1988:1011-2.

Daeniker HU, Druey J. Heilmittelchemische studien in der heterocyclischen reihe. 18. Mitteilung. über polymethylen-bis-sydnone und polymethylen-bis-hydrazine. Helvetica Chim Acta 1957;40:918-32.

Preston PN, Turnbull K. Approaches to the synthesis of compounds containing fused mesoionic rings. J Chem Soc, Perkin Trans 1977. p. 1229-33.

Stewart FHC. Cyclodehydration of αα′-di-(N-2-cyanoethyl-N-nitrosoamino)-glutaric Acid. J Chem Soc (Resumed) 1963. p. 2099-100.

Stewart FHC. Hydrolysis of N-alkyl-N-nitros-aspartic anhydrides. J Chem Soc (Resumed); 1963. p. 3158-60.

Azarifar D, Ghasemnejad-Bosra H, Ghorbani-Vaghei R, Tajbaksh M. N,N,N',N'-tetrabromobenzene-1, 3-disolfonamide (TBBDS) as an efficient promoter for one-pot conversion of N-arylglycines to sydnones in the presence of NaNO2/Ac2O under neutral conditions. Heterocycles 2006;68:2343-7.

Azarifar D, Ghasemnejad-Bosra H. Catalytic activity of 1,3-dibromo-5,5-dimethylhydantoin (DBH) in the one-pot transformation of N-arylglycines to N-arylsydnones in the presence of NaNO2/Ac2O under neutral conditions: subsequent bromination of these sydnones to their 4-bromo derivatives. Synthesis 2006;7:1123-6.

Kier LB, Roche E. Molecular orbital calculations of the electronic structure of the sydnones. J Pharm Sci 1966;55:807-12.

Barnighausen H, Jellinek F, Munnik Jt, Vos A. The structure of N-(p-bromophenyl) sydnone. Acta Cryst 1963;16:471-5.

Wang Y, Lee PL, Yeh MH. Structure of 3-(p-ethoxyphenyl) sydnone , C10H10N2O3, and 3-(p-tolyl) sydnone , C9H8N2O2. Acta Cryst Sect C: Cryst Str Comm 1984;40:1226-8.

Greco CV, O'Reilly BP. Mesoionic compounds vi metallation of sydnones. An estimation of acidity. J Heterocycl Chem 1970;7:1433-4.

Fan JM, Wang Y, Ueng CH. Electrostatic properties of sydnone derivatives. J Phys Chem 1993;97:8193-9.

Stewart FHC. The chemistry of the sydnones. Chem Rev 1964;64:129-47.

Kier LB, Roche EB. Medicinal chemistry of the mesoionic compounds. J Pharm Sci 1967;56:149-68.

Patel YM, Patel KC. Synthesis and biological evaluation of new sydnone based derivatives. J Saudi Chem Soc 2012;8:113-8.

Lawson KD, Brey WS, Kier LB. Hydrogen chemical shifts of 3-alkyl and 3-phenyl sydnones. J Am Chem Soc 1964;86:463-5.

Savaliya PP, Akbari VK, Patel KC. Studies on synthesis of some new sydnone containing compounds and their biological activities. Chem Sci Trans 2013;2:589-97.

Foster RS, Adams H, Jakobi H, Harrity JPA. Synthesis of 4-Fluoromethylsydnones and their participation in alkyne cycloaddition reactions. J Org Chem 2013;78:4049-64.

Greco CV, Tobias J, Kier LB. Acylation of 3‐phenylsydnone with carboxylic acids and phosphorus pentoxide. J Heterocycl Chem 1967;4:160-2.

Zhang ZB, Wu YR, Yin CL. The efficient synthesis of new sydnones containing fused ring. Synth Comm 2002;32:2203-7.

Tullis SA, Turnbull K. Acylation and aroylation of 3-phenylsydnone. Synth Commun 1990;20:3137-44.

Turnbull K, George JC. Acylation of sydnones with acetic anhydride in the presence of montmorillonite K-10. Synth Commun 1996;26:2757-64.

Ghasemnejad-Bosra H, Haghdadi M, Gholampour-Azizi I. N-bromosuccinimide (NBS) as promoter for acylation of sydnones in the presence of acetic anhydride under neutral conditions. Heterocycles 2008;75:391-5.

Mahoney J, Turnbull K, Cubberley M. Bismuth triflate-catalyzed friedel-crafts acylations of sydnones. Synth Comm 2012;42:3220-9.

Balaguer AM, Selhorst R, Turnbull K. Metal triflate-catalyzed friedel-crafts acetylation of 3-phenylsydnone. Synth Commun 2013;43:1626-32.

Balaguer AM, Rumple AC, Turnbull K. Bismuth triflate catalyzed friedel-crafts acylation of 3-phenyl-and 3-(2-carboalkoxyphenyl)sydnones under microwave irradiation. Org Prep Proced Int 2014;46:363-9.

Thoman CJ, Voaden DJ, Hunsberger IM. Direct formylation of sydnones. J Org Chem 1964;29:2044-5.

Yeh MY, Tien HJ, Huang LY, Chen MH. Sydnone compounds. Xx. The Synthesis and the schmidt reaction of 4-formyl-3-arylsydnone. J Chinese Chem Soc 1983;30:29-37.

Greco CV, Mehta JR. Meso‐Ionic compounds. XI, photochromic 4‐halogeno‐3‐(3‐pyridyl) sydnones. J Heterocycl Chem 1979;16:1059-60.

Dumitraşcu F, Drâghici C, Dumitrescu D, Tarko L, Râileanu D. Direct iodination of sydnones and their cycloadditions to form 5‐iodopyrazoles. Liebigs Annalen 1997;1997:2613-6.

Dumitraşcu F, Mitan CI, Dumitrescu D, Drăghici C, Căproiu MT. Steric effects on the sydnones reactivity. New sydnones and pyrazoles. Arkivoc 2002;2:80-6.

Nashashibi IF, Tumey JM, Owens BL, Turnbull K. Chlorination of 3-arylsydnones with iodine monochloride. Org Prep Proced Int 2017;49:59-63.

Fuchigami T, Ching-Sy C, Tsutomu N, Mou-Yung Y, Hsien-Ju T. Synthesis of sydnone compounds substituted by heteroatom groups at the 4-positions. Bull Chem Soc Japan 1986;59:483-6.

Fuchigami T, Ching-Sy C, Tsutomu N, Mou-Yung Y, Hsien-Ju T. Preparation of sydnone compounds substituted by thio and seleno functional groups at the 4-positions. Bull Chem Soc Japan 1986;59:487-91.

Turnbull K, Krein DM. The sydnone ring as an Ortho-director of lithiation. Dilithiation of 3-phenylsydnone and trapping by electrophiles. Tetrahedron Lett 1997;38:1165-8.

Turnbull K, Sun C, Krein DM. The sydnone ring as an Ortho-director of lithiation 2. Dilithiation of 3-phenylsydnone and regiospecific O-aryl acylation using N-methoxy-N-methylamides. Tetrahedron Lett 1998;39:1509-12.

Turnbull K, Krein DM. Formation of 4-Hydroxy-4-substituted Sydno[3,4-a](4H)indoles via dilithiation of 3-(2-Bromophenyl)sydnone. Synthesis 1996;10:1183- 4.

Turnbull K, Krein DM. Sydnone ring as an Ortho-director of lithiation, 3: one-pot regiospecific O-acylation and subsequent sydnone 4-substitution. Synth Commun 2009;39:2852-8.

Wagner H, Hill JB. Antiinflammatory sydnones 1. J Med Chem 1974;17:1337-8.

Hill JB, Ray RE, Wagner H, Aspinall RL. Antiinflammatory sydnones 2. J Med Chem 1975;18:50-3.

Upadhya KG, Badami BV, Puranik GS, Biradar VN, Nanjappa S. Synthesis and antiinflammatory activity of 3-substituted 4-(4'-Thiazolyl)-sydnones. Arch Pharm 1980;313:684-8.

Satyabarayana K, Rao MNA. Synthesis of 4-[5-(Substituted aryl)-4,5-dihydro-1H-pyrazol-3-yl]-3-phenyl-sydnones as antiinflammatory, antiarthritic and analgesic agents. Eur J Med Chem 1995;30:641-5.

Deshpande SR, Pai KV, Pai RS. Design and synthesis of certain mesoionic sydnonyl styrylketones as potential nonsteroidal antiinflammatory agents. Arzneimittel-Forschung/Drug Res 2011;61:180-5.

Deshpande SR, Pai KV. Fluorine bearing sydnones with styryl ketone group: synthesis and their possible analgesic and anti-inflammatory activities. J Enzyme Inhib Med Chem 2012;27:241-8.

Nithinchandra, Kalluraya B, Aamir S, Shabaraya AR. Regioselective reaction: synthesis, characterization and pharmacological activity of some new mannich and schiff bases containing sydnone. Eur J Med Chem 2012;54:597-604.

Kamble RR, Belgur SS, Aladkatti R, Khazi IA. Synthesis and evaluation of benzophenone oximes derivatized with sydnone as inhibitors of secretory phospholipase A2 with anti-inflammatory activity. Chem Pharm Bull 2009;57:16-21.

Bizetto EL, Noleto GR, Echevarria A, Canuto AV, Cadena SM. Effect of sydnone SYD-1 on certain functions of LPS-stimulated macrophages. Mol Cel Biochem 2012;360:15-21.

Grynberg N, Gomes R, Shinzato T, Echevarria A, Miller J. Some new aryl-sydnones: effects on murine tumours. Anticancer Res 1992;12:1025-8.

Anto RJ, Kuttan G, Kuttan R, Sathyanarayana K, Rao MNA. Tumor-reducing and antioxidant activities of sydnone-substituted chalcones. J Clin Biochem Nutr 1994;17:73-80.

Dunkley CS, Thoman CJ. Synthesis and biological evaluation of a novel phenyl substituted sydnone series as potential antitumor agents. Bioorg Med Chem Lett 2003;13:2899-901.

Butković K, Marinić Ž, Šindler-Kulyka M. Synthesis of 3-(o-Stilbenyl)-sydnone and 3-(o-Stilbenyl)-4-substituted-sydnone derivatives and their antitumor evaluation. Arkivoc 2011;10:1-15.

Tegginamath G, Kamble RR, Taj T, Kattimani PP, Meti GY. Synthesis of novel imidazo[2,1-B][1,3,4]thiadiazoles appended to sydnone as anticancer agents. Med Chem Res 2013;22:4367-75.

Shih MH, Chen JC, Lin GL, Lin TT, Sun MH. Novel synthesis of palladium (II) complexes derived from 3-arylsydnone-4-carbaldehyde N-phenylthiosemicarbazones and biological activity. J Pharm Pharmacol 2014;66:73-83.

Halila GC, de Oliveira MB, Echevarria A, Belém AC, Rocha ME, Carnieri EG, et al. Effect of sydnone SYD-1, a mesoionic compound, on energy-linked functions of rat liver mitochondria. Chem Biol Interact 2007;169:160-70.

Gozzi GJ, Pires AD, Martinez GR, Rocha ME, Noleto GR, Echevarria A, et al. The antioxidant effect of the mesoionic compound SYD-1 in mitochondria. Chem Biol Interact 2013;205:181-7.

Galuppo LF, dos Reis Lívero FA, Martins GG, Cardoso CC, Beltrame OC, Klassen LMB, et al. Sydnone 1: a mesoionic compound with antitumoral and haematological effects in vivo. Basic Clin Pharmacol Toxicol 2016;119:41-50.

Naito T, Nakagawa S, Takahashi K, Masuko K, Fujisawa K. Synthesis of 6-aminopenicillanic acid derivatives 3. 6-(3-Substituted-sydnone-4-carboxamido)-penicillanates. J Antibiot 1968;21:290.

Moustafa MAA, Eisa HM. Synthesis and antimicrobial activity of 3‐(Substituted‐phenyl)‐sydnones. Arch Pharm 1992;325:397-401.

Hegde JC, Girisha KS, Adhikari A, Kalluraya B. Synthesis and antimicrobial activities of a new series of 4-S-[4-amino-5-oxo-6-substituted benzyl-4,5-dihydro-1,2,4-triazin-3-yl]mercaptoacetyl-3-arylsydnones. Eur J Med Chem 2008;43:2831-4.

Savaliya PP, Akbari VK, Modi JA, Patel KC. Synthesis, characterization, and antimicrobial screening of some mannich base sydnone derivatives. Med Chem Res 2013;22:5789-97.

Rahiman MA, Kalluraya B. Synthesis, characterization, antimicrobial and anthelmintic activity of some sydnone-N-mannich bases. J Indian Counc Chem 2008;25:10-4.

Asundaria ST, Patel KC. Synthesis and characterization of some sulfonamide based bis-sydnones and their in vitro antimicrobial activity. Indian J Chem Sect B: Org Chem Incl Med Chem 2010;49:960-4.

Asundaria ST, Patel KC. Synthesis, Characterization, and Antimicrobial Studies of Bissydnones Based on 4,4'-Diaminodiphenyl Methane. Synth Comm 2010;40:1899-906.

Asundaria ST, Patel KC. Synthesis, characterization and antimicrobial activity of thiazole, benzothiazole and pyrimidine derivatives bearing sydnone moieties. Pharm Chem J 2012;45:725-31.

Asundaria ST, Pannecouque C, De Clercq E, Patel KC. Sydnone sulfonamide derivatives as antibacterial, antifungal, antiproliferative and anti-HIV agents. Pharm Chem J 2014;48:260-8.

Patel YM, Patel KC. Synthesis and biological evaluation of new sydnone based derivatives. J Saudi Chem Soc 2015;19:193-9.

Bhosale SK, Deshpande SR, Wagh RD. Ultrasound assisted one pot synthesis, spectral, antimicrobial and antioxidant studies of novel 4-[1-oxo-3-(substituted phenyl)-2-propenyl]-3-substituted phenyl sydnones. Asian J Chem 2015;27:3063-8.

Shih MH, Ke FY. Syntheses and evaluation of antioxidant activity of sydnonyl substituted thiazolidinone and thiazoline derivatives. Bioorg Med Chem 2004;12:4633-43.

Shih MH, Su YS, Wu CL. Syntheses of aromatic substituted hydrazino-thiazole derivatives to clarify structural characterization and antioxidant activity between 3-arylsydnonyl and aryl substituted hydrazino-thiazoles. Chem Pharm Bull 2007;55:1126-35.

Nyberg WH, Cheng CC. 3-Piperonylsydnone. A new type of antimalarial agent. J Med Chem 1965;8:531-3.

Boots SG, Cheng CC. Structural modification studies of 3-piperonylsydnone i. synthesis of piperonyl-substituted pyrazoles, isoxazoles, triazoles, oxadiazoles and thiadiazoles. J Heterocycl Chem 1967;4:272-83.

Popoff IC, Singhal GH, Engle AR. Antimalarial agents 7. Compounds related to 4,4'-Bis(aminophenyl) sulfone. J Med Chem 1971;14:550-1.




About this article

Title

MESOIONIC SYDNONE: A REVIEW IN THEIR CHEMICAL AND BIOLOGICAL PROPERTIES

Keywords

Sydnone, Mesoionic, Heterocycles, Anticancer, Antimicrobial, Anti-inflammatory

DOI

10.22159/ijpps.2017v9i8.18774

Date

01-08-2017

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 9, Issue 8, 2017 Page: 1-9

Online ISSN

0975-1491

Statistics

219 Views | 0 Downloads

Authors & Affiliations

Abdualrahman Mohammed Abdualkader
Pharmaceutical Chemistry Department, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia
Malaysia

Muhammad Taher
Pharmaceutical Technology Department, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia

Nik Idris Nik Yusoff
Pharmaceutical Chemistry Department, Faculty of Pharmacy, International Islamic University Malaysia, Kuantan, Pahang, Malaysia


Article Tools



Refbacks

  • There are currently no refbacks.