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Multifunctional toxin phospholipase A2 (PLA2) in Naja oxiana venom, a promising target for 2,5-disubstituted-1,3,4-oxadiazole derivatives


Affiliations
1 Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan
2 Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan
3 Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan; Institute of Fundamental Medicine and Biology, Department of Genetics, Kazan Federal University, Kazan 420008, Russia
 

The present work is designed to synthesize 2,5-disub­stituted-1,3,4-oxadiazole derivatives 5a–5d as snake venom phospholipase A2 (PLA2) inhibitors. The snake venom was isolated from Naja oxiana by pressing their glands below eyes to perform anti-PLA2 activity. The compounds 5a–5d showed good PLA2 inhibitory potential, especially 5d exhibited excellent activity having IC50 value 0.002 mM (0.01 > p > 0.001) followed by 5c having IC50 value 0.003 mM (0.01 > p > 0.001). Compounds 5a and 5b have IC50 values 0.027 mM (p < 0.001) and 0.014 mM (p < 0.001) respectively. The docking results showed that all compounds have binding interactions with amino acid residues in active binding site. They have good binding affinities, particularly 5d has binding energy –6.8 kcal/mol compared to other analogues. On the basis of dry and wet lab results, it may proposed that 5d may act as a potent inhibitor of PLA2 in N. oxiana venom.

Keywords

Naja oxiana, phospholipase A2 inhibitors, oxadiazoles, snake bite envenomation.
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  • Multifunctional toxin phospholipase A2 (PLA2) in Naja oxiana venom, a promising target for 2,5-disubstituted-1,3,4-oxadiazole derivatives

Abstract Views: 300  |  PDF Views: 145

Authors

Rabia Tariq
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan
Ejaz Ul Hassan
Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan
Moeen Anjum
Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan
Muhammad Nawaz Khan
Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan
Zaman Ashraf
Department of Chemistry, Allama Iqbal Open University, Islamabad 44000, Pakistan
Fiaz Alam
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan
Abdul Mannan
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan
Muhammad Imran Amirzada
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan
Muhammad Hassham Hassan Bin Asad
Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan; Institute of Fundamental Medicine and Biology, Department of Genetics, Kazan Federal University, Kazan 420008, Russia

Abstract


The present work is designed to synthesize 2,5-disub­stituted-1,3,4-oxadiazole derivatives 5a–5d as snake venom phospholipase A2 (PLA2) inhibitors. The snake venom was isolated from Naja oxiana by pressing their glands below eyes to perform anti-PLA2 activity. The compounds 5a–5d showed good PLA2 inhibitory potential, especially 5d exhibited excellent activity having IC50 value 0.002 mM (0.01 > p > 0.001) followed by 5c having IC50 value 0.003 mM (0.01 > p > 0.001). Compounds 5a and 5b have IC50 values 0.027 mM (p < 0.001) and 0.014 mM (p < 0.001) respectively. The docking results showed that all compounds have binding interactions with amino acid residues in active binding site. They have good binding affinities, particularly 5d has binding energy –6.8 kcal/mol compared to other analogues. On the basis of dry and wet lab results, it may proposed that 5d may act as a potent inhibitor of PLA2 in N. oxiana venom.

Keywords


Naja oxiana, phospholipase A2 inhibitors, oxadiazoles, snake bite envenomation.

References





DOI: https://doi.org/10.18520/cs%2Fv123%2Fi5%2F650-657