Integracides: Tetracyclic Triterpenoids from Sp.-Their 5-Lipoxygenase Inhibitory Potential and Structure-Activity Relation Using In Vitro and Molecular Docking Studies

Overview

Journal Life (Basel)

Specialty Biology

Date 2022 Dec 23

PMID 36556460

Authors

Maan T Khayat

Khadijah A Mohammad

Gamal A Mohamed

Martin K Safo

Sabrin R M Ibrahim

Affiliations

Soon will be listed here.

Abstract

Inflammation is a complicated disorder that is produced as a result of consecutive processes. 5-LOX (5-lipoxygenase) is accountable for various inflammation mediators and leukotrienes synthesis, and its inhibition is the target of anti-inflammation therapeutics. Fungi have acquired enormous attentiveness because of their capability to biosynthesize novel bio-metabolites that reveal diversified bio-activities. A new tetracyclic triterpenoid, integracide L (), along with integracides B () and F (), were separated from -associated sp. (FS No. MAR2014). Their structures were verified utilizing varied spectral analyses. The isolated metabolites (-), alongside the earlier reported integracides G (), H (), and J (), were inspected for 5-LOX inhibition capacity. Interestingly, - possessed marked 5-LOX inhibition potentials with ICs ranging from 1.18 to 3.97 μM compared to zileuton (IC 1.17 µM). Additionally, molecular docking was executed to examine the interaction among these metabolites and 5-LOX, as well as to validate the in vitro findings. The docking study revealed their inhibitory activity interactions in the binding pocket. These findings highlighted the potential of integracides as lead metabolites for anti-inflammation drug discovery.

Citing Articles

Recent Updates on the Secondary Metabolites from Fungi and Their Biological Activities (Covering 2019 to 2024).

Amuzu P, Pan X, Hou X, Sun J, Jakada M, Odigie E J Fungi (Basel). 2024; 10(11).

PMID: 39590697 PMC: 11596042. DOI: 10.3390/jof10110778.

References

Misra S, Ghatak S, Patil N, Dandawate P, Ambike V, Adsule S . Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan-CD44v6 pathway and inducing cytotoxicity in colon cancer cells. Bioorg Med Chem. 2013; 21(9):2551-9. PMC: 3895464. DOI: 10.1016/j.bmc.2013.02.033. View

Sastry G, Adzhigirey M, Day T, Annabhimoju R, Sherman W . Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des. 2013; 27(3):221-34. DOI: 10.1007/s10822-013-9644-8. View

Koeberle A, Henkel A, Verhoff M, Tausch L, Konig S, Fischer D . Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G. Molecules. 2018; 23(2). PMC: 6017322. DOI: 10.3390/molecules23020506. View

Friesner R, Banks J, Murphy R, Halgren T, Klicic J, Mainz D . Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004; 47(7):1739-49. DOI: 10.1021/jm0306430. View

Macias-Rubalcava M, Sanchez-Fernandez R . Secondary metabolites of endophytic Xylaria species with potential applications in medicine and agriculture. World J Microbiol Biotechnol. 2016; 33(1):15. DOI: 10.1007/s11274-016-2174-5. View

Henderson Jr W . The role of leukotrienes in inflammation. Ann Intern Med. 1994; 121(9):684-97. DOI: 10.7326/0003-4819-121-9-199411010-00010. View

Zhang H, Song Y, Tan R . Biology and chemistry of endophytes. Nat Prod Rep. 2006; 23(5):753-71. DOI: 10.1039/b609472b. View

Adebayo E, Azeez M, Alao M, Oke A, Aina D . Fungi as veritable tool in current advances in nanobiotechnology. Heliyon. 2021; 7(11):e08480. PMC: 8640478. DOI: 10.1016/j.heliyon.2021.e08480. View

Tabata N, Tomoda H, Yamaguchi Y, Masuma R, Bamberger M, Omura S . Inhibition of cholesteryl ester transfer protein by fungal metabolites, L681,512. J Antibiot (Tokyo). 2000; 52(11):1042-5. DOI: 10.7164/antibiotics.52.1042. View

10.

Lewis R, Austen K, Soberman R . Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med. 1990; 323(10):645-55. DOI: 10.1056/NEJM199009063231006. View

11.

Charlier C, Michaux C . Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. Eur J Med Chem. 2003; 38(7-8):645-59. DOI: 10.1016/s0223-5234(03)00115-6. View

12.

de Souza J, Curcino Vieira I, Rodrigues-Filho E, Braz-Filho R . Terpenoids from endophytic fungi. Molecules. 2011; 16(12):10604-18. PMC: 6264667. DOI: 10.3390/molecules161210604. View

13.

Shankar A, Sharma K . Fungal secondary metabolites in food and pharmaceuticals in the era of multi-omics. Appl Microbiol Biotechnol. 2022; 106(9-10):3465-3488. PMC: 9095418. DOI: 10.1007/s00253-022-11945-8. View

14.

Ge J, Liu Z, Zhong Z, Wang L, Zhuo X, Li J . Natural terpenoids with anti-inflammatory activities: Potential leads for anti-inflammatory drug discovery. Bioorg Chem. 2022; 124:105817. DOI: 10.1016/j.bioorg.2022.105817. View

15.

Brill G, Kati W, Montgomery D, Karwowski J, Humphrey P, Jackson M . Novel triterpene sulfates from Fusarium compactum using a rhinovirus 3C protease inhibitor screen. J Antibiot (Tokyo). 1996; 49(6):541-6. DOI: 10.7164/antibiotics.49.541. View

16.

Friesner R, Murphy R, Repasky M, Frye L, Greenwood J, Halgren T . Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem. 2006; 49(21):6177-96. DOI: 10.1021/jm051256o. View

17.

Adeleke B, Babalola O . The plant endosphere-hidden treasures: a review of fungal endophytes. Biotechnol Genet Eng Rev. 2021; 37(2):154-177. DOI: 10.1080/02648725.2021.1991714. View

18.

Slusarczyk J, Adamska E, Czerwik-Marcinkowska J . Fungi and Algae as Sources of Medicinal and Other Biologically Active Compounds: A Review. Nutrients. 2021; 13(9). PMC: 8464797. DOI: 10.3390/nu13093178. View

19.

Steele V, Holmes C, Hawk E, Kopelovich L, Lubet R, Crowell J . Lipoxygenase inhibitors as potential cancer chemopreventives. Cancer Epidemiol Biomarkers Prev. 1999; 8(5):467-83. View

20.

Xu J, Yi M, Ding L, He S . A Review of Anti-Inflammatory Compounds from Marine Fungi, 2000-2018. Mar Drugs. 2019; 17(11). PMC: 6891400. DOI: 10.3390/md17110636. View