Expeditious Synthesis, Antimicrobial and Antimalarial Activities of Novel Heterocycles Bearing Imidazole-oxadiazole Based Hybrid Pharmacophores

 

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Abstract

A facile synthesis of 2-substituted-5-amino-oxadiazole derivatives has been achieved by refluxing/sonicating a mixture of semicarbazide with various aromatic acids in conc. sulphuric acid alone. The isolated products were further condensed with p-dimethylaminobenzaldehyde/p-hydroxybenzaldehyde to obtain respective imino derivatives. Finally, some potentially biologically active imidazole analogues were obtained by reacting ammonium acetate and 5-bromoisatin with the synthesized imino products. All the newly synthesized compounds were thoroughly characterized by standard analytical techniques. These imidazole-oxadiazole hybrid compounds were also evaluated for their antimicrobial and antimalarial activities. The compounds all exhibited moderate to significant antimicrobial activity (6–10 mm, zone of inhibition) and promising antimalarial activity (IC₅₀ 0.037–0.100 µM). This report entails a detailed synthetic procedure, spectroscopic elucidation and activities of the synthesized compounds.

^* Both the authors contributed equally and both are co-first authors

• References

• 1 Karthikeyan MS, Prasad DJ, Mahalinga M et al. Antimicrobial studies of 2,4-dichloro-5-fluorophenyl containing oxadiazoles. Eur J Med Chem 2008; 43: 25-31
  CrossrefPubMedGoogle Scholar
• 2 Patel RV, Kumari P, Chikhalia KH. New Quinolinyl–1,3,4–Oxadiazoles: Synthesis, In Vitro Antibacterial. Antifungal and Antituberculosis Studies. Med Chem 2013; 9: 596-607
  PubMedGoogle Scholar
• 3 Bezerra NMM, De Oliveira SP, Srivastava RM et al. Synthesis of 3-aryl-5-decapentyl-1,2,4-oxadiazoles possessing antiinflammatory and antitumor properties. Farmaco 2005; 60: 955-960
  CrossrefPubMedGoogle Scholar
• 4 Gupta A, Kashaw SK, Jain N et al. Design and synthesis of some novel 3-[5-(4-substituted) phenyl-1,3,4-oxadiazole-2yl]-2-phenylquinazoline-4(3H)-ones as possible anticonvulsant agent. Med Chem Res 2011; 20: 1638-1642
  CrossrefPubMedGoogle Scholar
• 5 El-Emam AA, Al-Deeb OA, Al-Omar MA et al. Synthesis, antimicrobial, and anti-HIV-1 activity of certain 5-(1-adamantyl)-2-substituted thio-1,3,4-oxadiazoles and 5-(1-adamantyl)-3-substituted aminomethyl-1,3,4-oxadiazoline-2-thiones. Bioorg & Med Chem 2004; 12: 5107-5113
  CrossrefPubMedGoogle Scholar
• 6 Maftei CV, Fodor E, Jones PG et al. Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties. Beilstein J Org Chem 2013; 9: 2202-2215
  CrossrefPubMedGoogle Scholar
• 7 Bhandari SV, Bothara KG, Raut MK et al. Design, synthesis and evaluation of antiinflammatory, analgesic and ulcerogenicity studies of novel S-substituted phenacyl-1,3,4-oxadiazole-2-thiol and Schiff bases of diclofenac acid as nonulcerogenic derivatives. Bioorg Med Chem 2008; 16: 1822-1831
  CrossrefPubMedGoogle Scholar
• 8 de Oliveira CS, Lira BF, Barbosa-Filho JM et al. Synthetic Approaches and Pharmacological Activity of 1,3,4-Oxadiazoles: A Review of the Literature from 2000–2012. Molecules 2012; 17: 10192-10231
  CrossrefPubMedGoogle Scholar
• 9 Barakat A, Al-Majid AM, Al-Qahatany FM et al. Synthesis, characterisation and antimicrobial activities of novel pharmacophore incorporating imidazoline oxadiazoline scafold Bull. Korean Chem Soc 2014; 35: 562-568
  CrossrefPubMedGoogle Scholar
• 10 Vereshchagin AN, Elinson MN, Nasybullin RF et al. Protocol for the Synthesis of Medicinally Relevant 4H-Pyrano[3,2-c]quinoline Scaffold. Helvetica Chimica Acta 2015; 98: 1104-1114
  CrossrefPubMedGoogle Scholar
• 11 Hussein EM, Khairou KS. Sonochemistry: synthesis of bioactive heterocycles. Synthetic Comm 2014; 44: 2155-2191
  CrossrefPubMedGoogle Scholar
• 12 Yearick K, Ekoue-Kovi K, Iwaniuk D et al. de Dios AC, Roepe PD, Wolf C. Overcoming Drug Resistance to Heme-Targeted Antimalarials by Systematic Side Chain Variation of 7-Chloro-4-aminoquinolines. J Med Chem 2008; 51: 1995-1998
  CrossrefPubMedGoogle Scholar
• 13 Robert A, Benoit-Vical F, Dechy-Cabaret O et al. From classical antimalarial drugs to new compounds based on the mechanism of action of artemisinin. Pure Appl Chem 2001; 73: 1173-1188
  CrossrefPubMedGoogle Scholar
• 14 Pace A, Pierro P. The new era of 1,2,4-oxadiazoles. Org Biomol Chem 2009; 7: 4337-4348
  CrossrefPubMedGoogle Scholar
• 15 Pandey VK, Negi HS, Joshi MN et al. Synthesis and biological activity of some new benzophenothiazines. Indian J Chem 2003; 42B: 206-210
  PubMedGoogle Scholar
• 16 Wolkenberg SC, Wisnoski DD, Leister WH et al. Efficient Synthesis of Imidazoles from Aldehydes and 1,2-Diketones Using Microwave Irradiation. Org Lett 2004; 6: 1453-1456
  CrossrefPubMedGoogle Scholar
• 17 Rahman A, Choudhary MI, Thomsen WJ. Bioassay techniques for drug development. Harwood Academic Publishers; The Netherlands: 2001. p 16
  CrossrefGoogle Scholar
• 18 Jha A, Murthy YLN, Sanyal U et al. Rapid synthesis, characterization, anticancer and antimicrobial activity studies of substituted thiadiazoles and their dinucleating ligand metal complexes. Med Chem Res 2012; 21: 2548-2556
  CrossrefPubMedGoogle Scholar
• 19 Satayavivad J, Watcharasit P, Khamkong P et al. The pharmacodynamic study of a potent new antimalarial (MC1). Acta Trop 2004; 89: 343-349
  CrossrefPubMedGoogle Scholar
• 20 Lambros C, Vanderberg JP. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol 1979; 65: 418-420
  CrossrefPubMedGoogle Scholar
• 21 Holagh MV, oglu Maharramov AM, oglu Allahverdiyev MA et al. A one-pot efficient four-component reaction for the synthesis of 2-(arylamino)-2-(5-aryl-1-ethenyl-1,3,4-oxadiazol-2-yl)propyl benzoate (or 4-bromobenzoate) derivatives. Turk J Chem 2012; 36: 671-681
  PubMedGoogle Scholar
• 22 Issa YM, Hassib HB, Abdelaal HE. 1H NMR, 13C NMR and mass spectral studies of some Schiff bases derived from 3-amino-1,2,4-triazole. Spectrochimica Acta. 2009; Part A 74: 902-910
  CrossrefPubMedGoogle Scholar
• 23 Anjaneyula Y, Rao RP. Preparation, characterization and antimicrobial activity studies on some ternary complexes of Cu(II) with acetyl acetone and various salicylic acids. Synth React Inorg Met Org Chem 1986; 16: 257-272
  CrossrefPubMedGoogle Scholar

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