Match!

Modulation of aromatase by natural compounds—A pharmacophore guided molecular modelling simulations

Published on Jan 1, 2019in South African Journal of Botany1.50
· DOI :10.1016/j.sajb.2018.06.019
Shailima Rampogu7
Estimated H-index: 7
(Gyeongsang National University),
Chanin Park8
Estimated H-index: 8
(Gyeongsang National University)
+ 4 AuthorsKeun Woo Lee30
Estimated H-index: 30
(Gyeongsang National University)
Abstract
Abstract Globally, breast cancer is one of the primary reasons of death noticed in women. Despite continuous efforts to formulate effective treatments, search to identify promising therapeutics is underway. Consequently, a drug with low toxicity, high efficacy, and which can escape resistance mechanism is in a high demand. Natural compounds are bestowed with several medicinal properties demonstrating low toxicity. Therefore, the current research focuses on the use of several plant- derived chemical compounds against aromatase, a validated drug target for breast cancer. Correspondingly, employing the known inhibitors, a 3D QSAR pharmacophore model was generated and was subsequently validated. Using the three-featured pharmacophore as the 3D query, the alkaloids, flavonoids, coumarins and the AfroDB were scrupulously examined to retrieve the compounds with inhibitory activities complemented by the pharmacophore model. The obtained compounds were subjected to molecular docking studies executed employing the Cdocker accessible on discovery studio v4.5. The resultant ideal poses from the largest cluster conferred with key reside interactions and higher dock scores than the reference and the Food and Drug Administration (FDA) approved drugs were escalated to molecular dynamics simulation studies conducted employing GROMACS v5.0.6 for 30 ns. Correspondingly, the Hits (ZINC95486358, ZINC95486354, and ZINC90711737) have displayed stable root mean square deviations, coupled by appropriate positioning at the active site displaying greater number of hydrogen bonds. Moreover, the Hits (ZINC95486358, ZINC95486354, and ZINC90711737) were noticed to anchor with various key residues essential for clamping the ligand at the binding pocket. Therefore, these findings guide us to determine that the identified Hits can act effectively against breast cancer, thereby increasing the life expectancy. Furthermore, they can assist as scaffolds for designing novel drugs that aid in curing the cancer.
  • References (85)
  • Citations (0)
References85
Newest
#1Shailima Rampogu (Gyeongsang National University)H-Index: 7
#2Ayoung Baek (Gyeongsang National University)H-Index: 7
Last.Keun Woo Lee (Gyeongsang National University)H-Index: 30
view all 4 authors...
12 CitationsSource
#1Sehan Lee (EPA: United States Environmental Protection Agency)H-Index: 5
#2Mace G. Barron (EPA: United States Environmental Protection Agency)H-Index: 37
3 CitationsSource
#1Toru Hanamura (Shinshu University)H-Index: 5
#2Shin-ichi Hayashi (Tohoku University)H-Index: 41
9 CitationsSource
#1Shailima Rampogu (Gyeongsang National University)H-Index: 7
#2Minky Son (Gyeongsang National University)H-Index: 8
Last.Keun Woo Lee (Gyeongsang National University)H-Index: 30
view all 8 authors...
9 CitationsSource
#1Ying Ma (Tianjin Medical University)H-Index: 3
#2Hong-Lian Li (Tianjin Medical University)H-Index: 4
Last.Run-Ling Wang (Tianjin Medical University)H-Index: 9
view all 6 authors...
4 CitationsSource
#1Hongjun Kang (Yunnan University)H-Index: 1
#2Xingqing Xiao (NCSU: North Carolina State University)H-Index: 5
Last.Xianghui Zeng (Yunnan University)H-Index: 18
view all 7 authors...
11 CitationsSource
#1Gokhan Zengin (Selçuk University)H-Index: 29
#2Zaahira Aumeeruddy-Elalfi (UoM: University of Mauritius)H-Index: 6
Last.Mohamad Fawzi Mahomoodally (UoM: University of Mauritius)H-Index: 13
view all 5 authors...
12 CitationsSource
#1Sandra Zárate (UBA: University of Buenos Aires)H-Index: 11
#2Tinna Stevnsner (AU: Aarhus University)H-Index: 34
Last.Ricardo Gredilla (Complutense University of Madrid)H-Index: 19
view all 3 authors...
22 CitationsSource
#1Ozra Tabatabaei-Malazy (Tehran University of Medical Sciences)H-Index: 13
#2Pooneh Salari (Tehran University of Medical Sciences)H-Index: 15
Last.Bagher Larijani (Tehran University of Medical Sciences)H-Index: 52
view all 4 authors...
40 CitationsSource
#1Carmen Streicher (University of Veterinary Medicine Vienna)H-Index: 4
#2Alexandra Heyny (University of Veterinary Medicine Vienna)H-Index: 1
Last.Reinhold G. Erben (University of Veterinary Medicine Vienna)H-Index: 25
view all 13 authors...
20 CitationsSource
Cited By0
Newest
View next paperSulfonanilide Derivatives in Identifying Novel Aromatase Inhibitors by Applying Docking, Virtual Screening, and MD Simulations Studies