Current Science

Open Access Open Access  Restricted Access Subscription Access

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.
User
Notifications
Font Size

  • Luiselli, L., Sale, L., Akani, G. C. and Amori, G., Venomous snake abundance within snake species’ assemblages worldwide. Diversity, 2020, 12(2), 69.

  • Asad, M. H. H. B. et al., 5′-Nucleatidases of Naja naja kara-chiensis snake venom: their determination, toxicities and remedial approach by natural inhibitors (medicinal plants). Acta Pol. Pharm., 2016, 73(3), 667–673.

  • Alirol, E., Sharma, S. K., Bawaskar, H. S., Kuch, U. and Chappuis, F., Snake bite in South Asia: a review. PLoS Negl. Trop. Dis., 2010, 4(1), e603.

  • Masroor, R., Khisroon, M. and Jablonski, D., A case study on illegal reptile poaching from Balochistan. Pakistan. Herpetozoa, 2020, 33, 67.

  • Ebrahim, K., Vatanpour, H., Zare, A., Shirazi, F. H. and Nakhjavani, M., Anticancer activity a of Caspian cobra (Naja oxiana) snake venom in human cancer cell lines via induction of apoptosis. Iran. J. Pharm. Res., 2016, 15 (Suppl.), 101.

  • Asad, M. H. H. B. et al., Proteomics study of southern Punjab Paki-stani cobra (Naja naja: formerly Naja naja karachiensis) venom. Toxicol. Environ. Chem., 2019, 101(1–2), 91–116.

  • Asad, M. H. H. B. et al., Phospholipases A2: enzymatic assay for snake venom (Naja naja karachiensis) with their neutralization by medicinal plants of Pakistan. Acta Pol. Pharm., 2014, 71(4), 625–630.

  • Murakami, M., Taketomi, Y., Miki, Y., Sato, H., Hirabayashi, T. and Yamamoto, K., Recent progress in phospholipase A2 research: from cells to animals to humans. Prog. Lipid Res., 2011, 50(2), 152–192.

  • Six, D. A. and Dennis, E. A., The expanding superfamily of phos-pholipase A2 enzymes: classification and characterization. Biochim. Biophys. Acta, 2000, 1488(1–2), 1–19.

  • Montecucco, C., Gutierrez, J. M. and Lomonte, B., Cellular patho-logy induced by snake venom phospholipase A2 myotoxins and neurotoxins: common aspects of their mechanisms of action. Cell. Mol. Life Sci., 2008, 65(18), 2897–2912.

  • Ahmed, S. M., Ahmed, M., Nadeem, A., Mahajan, J., Choudhary, A. and Pal, J., Emergency treatment of a snake bite: pearls from literature. J. Emerg. Trauma Shock, 2008, 1(2), 97.

  • Trim, S. A., Trim, C. M., Williams, H. F. and Vaiyapuri, S., The failures of ethnobotany and phytomedicine in delivering novel treatments for snakebite envenomation. Toxins, 2020, 12(12), 774.

  • Kumar, B., Kumar, A., Beheraand, A. K. and Raj, V., Latest update on pharmacological activities of 1,3,4-oxadiazole derivatives. J. Cell Sci. Ther., 2016, 7(233), 2.

  • Maslat, A. O., Abussaud, M., Tashtoush, H. and AL-Talib, M., Synthesis, antibacterial, antifungal and genotoxic activity of bis-1, 3,4-oxadiazole derivatives. Pol. J. Pharmacol., 2002, 54(1), 55–60.

  • Paruch, K., Popiołek, Ł. and Wujec, M., Antimicrobial and antipro-tozoal activity of 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines: a review. Med. Chem. Res., 2020, 29(1), 1–16.

  • Kumar, K. A., Jayaroopa, P. and Kumar, G. V., Comprehensive review on the chemistry of 1,3,4-oxadiazoles and their applications. Int. J. ChemTech Res., 2012, 4(4), 1782–1791.

  • Iqbal, Z., Iqbal, A., Ashraf, Z., Latif, M., Hassan, M. and Nadeem, H., Synthesis and docking studies of N‐(5‐(alkylthio)‐1,3,4‐oxadi-azol‐2‐yl) methyl) benzamide analogues as potential alkaline phos-phatase inhibitors. Drug Dev. Res., 2019, 80(5), 646–654.

  • Abas, M. et al., Designing novel anticancer sulfonamide based 2,5-disubstituted-1,3,4-thiadiazole derivatives as potential carbonic an-hydrase inhibitor. J. Mol. Struct., 2021, 1246, 131145.

  • Abbas, S. et al., Synthesis, characterization and biological evalua-tion of thiadiazole amide derivatives as nucleoside triphosphate di-phosphohydrolases (NTPDases) inhibitors. Bioorg. Chem., 2022, 118, 105456.

  • Iqbal, Z., Ashraf, Z., Hassan, M., Abbas, Q. and Jabeen, E., Substi-tuted phenyl[(5-benzyl-1,3,4-oxadiazol-2-yl)sulfanyl]acetates/aceta-mides as alkaline phosphatase inhibitors: synthesis, computational studies, enzyme inhibitory kinetics and DNA binding studies. Bioorg. Chem., 2019, 90, 103108.

  • Tan, N. H., Tan, C. S. and Khor, H. T., Isolation and characterization of the major phospholipase A2 from venom of Trimeresurus pupure-omaculatus (Short Pit Viper). Int. J. Biochem., 1989, 21(12), 1421–1426.


Abstract Views: 287

PDF Views: 135




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

Abstract Views: 287  |  PDF Views: 135

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