Quantum Chemical and Experimental Exploration of Biological Activity and Inhibitory Potential of New Acylated Oligosaccharides from Pistacia integerrima J. L. Stewart ex Brandis

Document Type : Research Article


1 Research Center for Advanced Materials Science, King Khalid University, P.O. Box 9004, Abha 61413, SAUDI ARABIA

2 Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, SAUDI ARABI

3 Department of Chemistry, University of Gujrat, 50700, PAKISTAN

4 Department of Chemistry, Faculty of Science, Ghazi University, Dera Ghazi Khan, PAKISTAN

5 Department of Pharmaceutical Chemistry, College of Pharmacy, University of Sargodha, PAKISTAN


The new biologically active integrisides A (1) and B (2) have been isolated from the methanolic extract of Pistacia integerrima J. L. Stewart ex Brandis. The antibacterial activity of both the integrities was tested against four pathogenic bacterial strains, two Gram-positive (Staphylococcus aureus, Streptococcus pyogenes) and two Gram-negative (Escherichia coli, Pseudomonas aeruginosa) as well as four fungal strains (Microsporum canis, Aspergillus clavatus, Candida albicans, and Candida glabrata). Both the isolated compounds showed significant results analogous with Imipenam and Miconazole standard drugs. Carbonic anhydrase-II inhibition of integriside A (1) and B (2) with IC50 value 1.56 µM and 2.85 µM respectively, as compared to standard drug acetazolamide (1.57 µM). Cholinesterase activity was carried out with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) IC50 values of integriside A (1) (8.6, 4.8) and B (2) (0.91, 2.5) were found as compared with standard galanthamine (0.05, 0.92) and Eserine (0.6, 8.7). Here, various molecular descriptors, frontier molecular orbitals (FMO), electron affinity (E.A), ionization potential (IP), molecular electrostatic potential (MEP), and Hirshfeld analysis were carried out to understand the active sites and biological active nature of the integrisides A (1) and B (2). The energy gap, MEP, Hirshfeld analysis, and reactivity descriptors values demonstrate that the integriside A (1) and B (2) retain decent reactivity, which is in good agreement with current experimental and quantum chemical studies.


Main Subjects

[1] Hussain M.S., Fareed S., Saba Ansari M., Rahman A., Ahmad I.Z., Saeed M., Current Approaches toward Production of Secondary Plant Metabolites, Journal of Pharmacy & Bioallied Sciences, 4(1): 10-     (2012).
[2] Bozorgi M., Memariani Z., Mobli M., Salehi Surmaghi M.H., Shams-Ardekani M.R., Rahimi R., Five Pistacia Species (P. Vera, P. Atlantica, P. Terebinthus, P. Khinjuk, and P. Lentiscus): A Review of Their Traditional Uses, Phytochemistry, and Pharmacology, The Scientific World Journal, 2013:   -   (2013).
[3] Moriana A., Memmi H., Centeno A., Martín-Palomo M., Corell M., Galindo A., Torrecillas A., Pérez-López D., Corrigendum to “Influence of Rootstock on Pistachio (Pistacia Vera L.) Water Relations”[Agricultural Water Management 202 (2018) 263-270], Agricultural Water Management, 216: 497 (2019).
[4] Tsokou A., Georgopoulou K., Melliou E., Magiatis P., Tsitsa E., Composition and Enantiomeric Analysis of the Essential Oil of the Fruits and the Leaves of Pistacia Vera from Greece, Molecules, 12(6): 1233-1239 (2007).
[5] Ullah Z., Mehmood R., Imran M., Malik A., Afzal R.A., Flavonoid Constituents of Pistacia Integerrima, Natural Product Communications, 7(8): 1934578X1200700813 (2012).
[6] Rauf A., Uddin G., Latif A., Muhammad N., Pistagremic Acid, a Novel Antimicrobial and Antioxidant Isolated from Pistacia Integerrima, Chemistry of Natural Compounds, 50(1): 97-99 (2014).
[7] Ullah Z., Mehmood R., Imran M., Malik A., Afzal R.A., New Acylated Oligosaccharides from Pistacia Integerrima, Natural Product Research, 27(21): 2027-2032 (2013).
[8] Noguera-Artiaga L., García-Romo J.S., Rosas-Burgos E.C., Cinco-Moroyoqui F.J., Vidal-Quintanar R.L., Carbonell-Barrachina Á.A., Burgos-Hernández A., Antioxidant, Antimutagenic and Cytoprotective Properties of Hydrosos Pistachio Nuts, Molecules, 24(23): 4362 (2019).
[9] Ahmad N.S., Waheed A., Farman M., Qayyum A., Analgesic and Anti-Inflammatory Effects of Pistacia Integerrima Extracts in Mice, Journal of Ethnopharmacology, 129(2): 250-253 (2010).
[10] Nocentini A., Supuran C.T., Carbonic Anhydrase Inhibitors as Antitumor/Antimetastatic Agents: A Patent Review (2008–2018), Expert Opinion on Therapeutic Patents, 28(10): 729-740 (2018).
[11] Burmaoglu S., Yilmaz A.O., Polat M.F., Kaya R., Gulcin İ., Algul O., Synthesis and Biological Evaluation of Novel Tris-Chalcones as Potent Carbonic Anhydrase, Acetylcholinesterase, Butyrylcholinesterase and Α-Glycosidase Inhibitors, Bioorganic Chemistry, 85: 191-197 (2019).
[12] Ekinci D., Karagoz L., Ekinci D., Senturk M., Supuran C.T., Carbonic Anhydrase Inhibitors: In Vitro Inhibition of Α Isoforms (HCA I, HCA II, BCA III, HCA IV) by Flavonoids, Journal of Enzyme Inhibition and Medicinal Chemistry, 28(2): 283-288 (2013).
[13] Angeli A., Tanini D., Capperucci A., Malevolti G., Turco F., Ferraroni M., Supuran C.T., Synthesis of Different Thio-Scaffolds Bearing Sulfonamide with Subnanomolar Carbonic Anhydrase II and IX Inhibitory Properties and X-Ray Investigations for Their Inhibitory Mechanism, Bioorganic Chemistry, 81: 642-648 (2018).
[14] Załuski D., Kuźniewski R., In Vitro Anti-AChE, Anti-BuChE, and Antioxidant Activity of 12 Extracts of Eleutherococcus Species, Oxidative Medicine and Cellular Longevity, 2016:    -     (2016).
[15] Atmaca U., Yıldırım A., Taslimi P., Çelik S.T., Gülçin İ., Supuran C.T., Çelik M., Intermolecular Amination of Allylic and Benzylic Alcohols Leads to Effective Inhibitions of Acetylcholinesterase Enzyme and Carbonic Anhydrase I and II Isoenzymes, Journal of Biochemical and Molecular Toxicology, 32(8): e22173 (2018).
[16] Espinosa S., Bec N., Larroque C., Ramírez J., Sgorbini B., Bicchi C., Gilardoni G., Chemical, Enantioselective, and Sensory Analysis of a Cholinesterase Inhibitor Essential Oil from Coreopsis Triloba S. ff.  Blake (Asteraceae), Plants, 8(11): 448 (2019).
[17] Rahman A.U., Ngounou F., Choudhary M.I., Malik S., Makhmoor T., Nur-E-Alam M., Zareen S., Lontsi D., Ayafor J., Sondengam B., New Antioxidant and Antimicrobial Ellagic Acid Derivatives from Pteleopsis Hylodendron, Planta Medica, 67(04): 335-339 (2001).
[18] Göçer H., Akincioğlu A., Göksu S., Gülçin İ., Supuran C.T., Carbonic Anhydrase and Acetylcholinesterase Inhibitory Effects of Carbamates and Sulfamoylcarbamates, Journal of Enzyme Inhibition and Medicinal Chemistry, 30(2): 316-320 (2015).
[19] Hİsar O., Beydemİr Ş., Gülçİn İ., Küfrevİoğlu Ö.İ., Supuran C.T., Effects of Low Molecular Weight Plasma Inhibitors of Rainbow Trout (Oncorhynchus Mykiss) on Human Erythrocyte Carbonic Anhydrase-II Isozyme Activity in Vitro and Rat Erythrocytes in Vivo, Journal of Enzyme Inhibition and Medicinal Chemistry, 20(1): 35-39 (2005).
[20] Ellman G.L., Courtney K.D., Andres Jr V., Featherstone R.M., A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity, Biochemical Pharmacology, 7(2): 88-95 (1961).
[21] Taslimi P., Osmanova S., Caglayan C., Turkan F., Sardarova S., Farzaliyev V., Sujayev A., Sadeghian N., Gulçin İ., Novel Amides of 1, 1‐Bis‐(Carboxymethylthio)‐1‐Arylethanes: Synthesis, Characterization, Acetylcholinesterase, Butyrylcholinesterase, and Carbonic Anhydrase Inhibitory Properties, Journal of Biochemical and Molecular Toxicology, 32(9): e22191 (2018).
[24] Sadasivam K., Jayaprakasam R., Kumaresan R., A DFT Study on the Role of Different OH Groups in the Radical Scavenging Process, J. Theor. Comput. Chem., 11(04): 871-893 (2012).
[25] Irfan A., Al-Zeidaneen F.K., Ahmed I., Al-Sehemi A.G., Assiri M.A., Ullah S., Abbas G., Synthesis, Characterization and Quantum Chemical Study of Optoelectronic Nature of Ferrocene Derivatives, Bull. Mater. Sci., 43(1): 45 (2020).
[27] Irfan A., Absorption Spectra and Electron Injection Study of the Donor Bridge Acceptor Sensitizers by Long Range Corrected Functional, Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 33(2): 11-28 (2014).
[28] Seif N., Farhadi A., Badri R., Kiasat A.R., An Experimental and Theoretical Study on Bicyclo-3,4-Dihydropyrimidinone Derivative: Synthesis and DFT Calculation, Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 38(6): 21-29 - (2019).
[29] Khalil Warad I., Al-Nuri M., Ali O., Abu-Reidah I.M., Barakat A., Ben Hadda T., Zarrouk A., Radi S., Touzani R., Hicham E., Synthesis, Physico-Chemical, Hirschfield Surface and DFT/B3lYP Calculation of Two New Hexahydropyrimidine Heterocyclic Compounds, Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 38(4): 59-68 (2019).
[30] Demirtaş G., Dege N., Ağar E., Şahin S., The Crystallographic, Spectroscopic and Theoretical Studies on (E)-2-[((4-Fluorophenyl)Imino)Methyl]-4-Nitrophenol and (E)-2-[((3-Fluorophenyl)Imino)Methyl]-4-Nitrophenol Compounds, Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 37(5): 55-65 (2018).
[31] Irfan A., Muhammad S., Chaudhry A.R., Al-Sehemi A.G., Jin R., Tuning of Optoelectronic and Charge Transport Properties in Star Shaped Anthracenothiophene-Pyrimidine Derivatives as Multifunctional Materials, Optik - Intern. J. Light Elect. Optics, 149(Supplement C): 321-331 (2017).
[32] Irfan A., Kalam A., Chaudhry A.R., Al-Sehemi A.G., Muhammad S., Electro-Optical, Nonlinear and Charge Transfer Properties of Naphthalene Based Compounds: A Dual Approach Study, Optik - Intern. J. Light Elect. Optics, 132: 101-110 (2017).
[33] Irfan A., Assiri M., Al-Sehemi A.G., Exploring the Optoelectronic and Charge Transfer Performance of Diaza[5]Helicenes at Molecular and Bulk Level, Org. Electron., 57: 211-220 (2018).
[34] Helander I., Nurmiaho-Lassila E.-L., Ahvenainen R., Rhoades J., Roller S., Chitosan Disrupts the Barrier Properties of the Outer Membrane of Gram-Negative Bacteria, International Journal of Food Microbiology, 71(2-3): 235-244 (2001).
[35] Rahman M.H., Shovan L.R., Hjeljord L.G., Aam B.B., Eijsink V.G., Sørlie M., Tronsmo A., Inhibition of Fungal Plant Pathogens by Synergistic Action of Chito-Oligosaccharides and Commercially Available Fungicides, Plos one, 9(4):    -     (2014).
[36] Gulcin I., Beydemir S., Phenolic Compounds as Antioxidants: Carbonic Anhydrase Isoenzymes Inhibitors, Mini-Reviews in Medicinal Chemistry, 13(3): 408-430 (2013).
[37] Morris J.C., Chiche J., Grellier C., Lopez M., Bornaghi L.F., Maresca A., Supuran C.T., Pouysségur J., Poulsen S.-A., Targeting Hypoxic Tumor Cell Viability with Carbohydrate-Based Carbonic Anhydrase IX and XII Inhibitors, Journal of Medicinal Chemistry, 54(19): 6905-6918 (2011).
[38] Winum J.-Y., Colinas P.A., Supuran C.T., Glycosidic Carbonic Anhydrase IX Inhibitors: A Sweet Approach against Cancer, Bioorganic & Medicinal chemistry, 21(6): 1419-1426 (2013).
[39] Akhtar M.N., Lam K.W., Abas F., Ahmad S., Shah S.A.A., Choudhary M.I., Lajis N.H., New Class of Acetylcholinesterase Inhibitors from the Stem Bark of Knema Laurina and their Structural Insights, Bioorganic & Medicinal Chemistry Letters, 21(13): 4097-4103 (2011).
[41] Geerlings P., De Proft F., Langenaeker W., Conceptual Density Functional Theory, Chemical Reviews, 103(5): 1793-1874 (2003).