Design and Synthesis of Novel 1,3,4-Oxadiazole Derivatives Bearing Azo Moiety as Biologically Significant Scaffolds

Author(s): Bilal Ahmad Khan*, Safeena Zafar, Ehsan Ullah Mughal*, Muhammad Naeem Ahmed, Syeda Shamila Hamdani, Tashfeen Akhtar, Ihsan-ul-Haq, Amina Sadiq, Khalid Mohammed Khan.

Journal Name: Letters in Drug Design & Discovery

Volume 15 , Issue 12 , 2018

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Abstract:

Introduction: Oxadiazoles having azo-functionality represent a new and an exciting class of physiologically active heterocyclic compounds. A number of molecules with these moieties have significant role in medicinal chemistry due to their diverse biological activities.

Methodology: A series of 1,3,4-oxadiazole-2-thiol derivatives bearing azo-moiety have been designed and synthesized by multistep reaction sequences staring from p-aminobenzoic acid by employing literature know procedures. These compounds were investigated for their antimicrobial, cytotoxic, α-amylase and protein kinase inhibitory and antileishmanial potential.

Results and Discussion: The newly synthesized compounds were characterized by spectroscopic techniques (IR, UV-Vis, NMR and MS). Antibacterial activity was investigated against four bacterial strains i.e. E. coli, P. aeruginosa, S. aureusand B. subtilis and good level of microbial inhibition was exhibited by most of the compounds with MIC 6.25 µg/mL. Brine Shrimp lethality assay revealed that the compound 31 is an excellent cytotoxic agent. (E)-5-(4-((4-Butoxyphenyl) diazenyl)phenyl)-1, 3,4-oxadiazole-2-thiol (21) showed good α-amylase inhibition (46.3± 0.45%) and (E)-2-(Decyloxythio)-5-(4-((propoxyphenyl)diazenyl)phenyl)-1,3,4-oxadiazole (30) exhibited excellent antileishmanial activity (88.4± 0.34%) at 10 µg/mL concentration. In case of protein kinase inhibition, remarkably, the oxadiazole-2-thiols (20-25) were found more active than the standard surfactinat tested concentration (25 µg/disc).

Conclusion: We have designed, synthesized and characterized an interesting series of biologically active oxadiazole bearing diazene moiety derivatives. Noteworthy, the presence of diazene functionality, polar heterocyclic moiety as well as hydrophobic alkyl chain is special feature of these compounds. These studies provide a basic idea to further explore these types of scaffolds as biologically potent molecules in drug design and development.

Keywords: Azo-compounds, 1, 3, 4-oxadiazole, biological activity, thioethers, cytotoxicity, enzyme inhibition, protein kinase inhibition.

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Article Details

VOLUME: 15
ISSUE: 12
Year: 2018
Page: [1346 - 1355]
Pages: 10
DOI: 10.2174/1570180815666180326152204
Price: $65

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