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

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

Volume: 15 Issue: 12

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

Affiliation:

• Department of Chemistry, University of Azad Jammu and Kashmir, Muzaffarabad 13100,Pakistan

• Department of Chemistry, University of Gujrat, Gujrat 50700,Pakistan

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

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.

Cite this article as:

Khan Ahmad Bilal *, Zafar Safeena , Mughal Ehsan Ullah *, Ahmed Naeem Muhammad , Hamdani Shamila Syeda , Akhtar Tashfeen , Ihsan-ul-Haq , Sadiq Amina and Khan Mohammed Khalid , Design and Synthesis of Novel 1,3,4-Oxadiazole Derivatives Bearing Azo Moiety as Biologically Significant Scaffolds, Letters in Drug Design & Discovery 2018; 15 (12) . https://dx.doi.org/10.2174/1570180815666180326152204