Targeting allosteric sites of human aromatase: a comprehensive <i>in-silico</i> and <i>in-vitro</i> workflow to find potential plant-based anti-breast cancer therapeutics

Alhadrami, Hani A.; Sayed, Ahmed M.; Melebari, Sami; Khogeer, Asim; Abdulaal, Wesam H.; Al-Fageeh, Mohamed B.; Algahtani, Mohammad; Rateb, Mostafa E.

doi:10.1080/14756366.2021.1937145

Cited by 12 publications

(5 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…cell migration) and colony formation assays were carried out using standard human cell lines (ATCC, USA) according to the previously reported methods. 33,70–72…”

Section: Methodsmentioning

confidence: 99%

“…In our ongoing efforts for the discovery of effective antiproliferative agents from natural products, [28][29][30][31][32][33][34][35] we found that EtOAc extract of P. peruviana ripe fruits (PEE) has a preferential antiproliferative effect against the human pancreatic cancer cell line PANC-1 (i.e. produced 69.44% growth inhibition at 5 µg extract; Fig.…”

Section: Chemical and Biological Characterization Of Peementioning

confidence: 99%

“…cell migration) and colony formation assays were carried out using standard human cell lines (ATCC, USA) according to the previously reported methods. 33,[70][71][72] In vitro MMP3 activity assay Magnolin was tested for its inhibitory activity against MMP-3. The enzyme inhibition assay was conducted according to the manufacturer's protocol (Abcam, Cat.…”

Section: Food and Function Papermentioning

confidence: 99%

See 2 more Smart Citations

Antiproliferative potential of Physalis peruviana-derived magnolin against pancreatic cancer: a comprehensive in vitro and in silico study

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…cell migration) and colony formation assays were carried out using standard human cell lines (ATCC, USA) according to the previously reported methods. 33,70–72…”

Section: Methodsmentioning

confidence: 99%

Section: Chemical and Biological Characterization Of Peementioning

confidence: 99%

Section: Food and Function Papermentioning

confidence: 99%

See 1 more Smart Citation

Antiproliferative potential of Physalis peruviana-derived magnolin against pancreatic cancer: a comprehensive in vitro and in silico study

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…As previously described, binding free energy estimation (∆G) and molecular dynamic simulations were performed [31][32][33]. These methods are described in detail in the supplementary file, pages S4, S5.…”

Section: Molecular Dynamic Simulation and Binding Free Energy Estimationmentioning

confidence: 99%

In Silico-Based Discovery of Natural Anthraquinones with Potential against Multidrug-Resistant E. coli

et al. 2022

Self Cite

View full text Add to dashboard Cite

E. coli is a Gram-negative bacterium that causes different human infections. Additionally, it resists common antibiotics due to its outer protective membrane. Natural products have been proven to be efficient antibiotics. However, plant natural products are far less explored in this regard. Accordingly, over 16,000 structures covering almost all African medicinal plants in AfroDb in a structural-based virtual screening were used to find efficient anti-E. coli candidates. These drug-like structures were docked into the active sites of two important molecular targets (i.e., E. coli’s Ddl-B and Gyr-B). The top-scoring hits (i.e., got docking scores < −10 kcal/mol) produced in the initial virtual screening (0.15% of the database structures for Ddl-B and 0.17% of the database structures for Gyr-B in the database) were further refined using molecular dynamic simulation-based binding free energy (ΔG) calculation. Anthraquinones were found to prevail among the retrieved hits. Accordingly, readily available anthraquinone derivatives (10 hits) were selected, prepared, and tested in vitro against Ddl-B, Gyr-B, multidrug-resistant (MDR) E. coli, MRSA, and VRSA. A number of the tested derivatives demonstrated strong micromolar enzyme inhibition and antibacterial activity against E. coli, MRSA, and VRSA, with MIC values ranging from 2 to 64 µg/mL. Moreover, both E. coli’s Ddl-B and Gyr-B were inhibited by emodin and chrysophanol with IC50 values comparable to the reference inhibitors (IC50 = 216 ± 5.6, 236 ± 8.9 and 0.81 ± 0.3, 1.5 ± 0.5 µM for Ddl-B and Gyr-B, respectively). All of the active antibacterial anthraquinone hits showed low to moderate cellular cytotoxicity (CC50 > 50 µM) against human normal fibroblasts (WI-38). Furthermore, molecular dynamic simulation (MDS) experiments were carried out to reveal the binding modes of these inhibitors inside the active site of each enzyme. The findings presented in this study are regarded as a significant step toward developing novel antibacterial agents against MDR strains.

show abstract

“…The binding free energy calculation (∆G) and molecular dynamic simulation were carried out as previously described [18,[29][30][31]. The Supplementary File has a detailed description of these methods (p. 19).…”

Section: Molecular Dynamic Simulation and Binding Free Energy Calcula...mentioning

confidence: 99%

Anticancer Potential of Green Synthesized Silver Nanoparticles of the Soft Coral Cladiella pachyclados Supported by Network Pharmacology and In Silico Analyses

et al. 2021

Self Cite

View full text Add to dashboard Cite

Cladiella-derived natural products have shown promising anticancer properties against many human cancer cell lines. In the present investigation, we found that an ethyl acetate extract of Cladiella pachyclados (CE) collected from the Red Sea could inhibit the human breast cancer (BC) cells (MCF and MDA-MB-231) in vitro (IC50 24.32 ± 1.1 and 9.55 ± 0.19 µg/mL, respectively). The subsequent incorporation of the Cladiella extract into the green synthesis of silver nanoparticles (AgNPs) resulted in significantly more activity against both cancer cell lines (IC50 5.62 ± 0.89 and 1.72 ± 0.36, respectively); the efficacy was comparable to that of doxorubicin with much-enhanced selectivity. To explore the mode of action of this extract, various in silico and network-pharmacology-based analyses were performed in the light of the LC-HRESIMS-identified compounds in the CE extract. Firstly, using two independent machine-learning-based prediction software platforms, most of the identified compounds in CE were predicted to inhibit both MCF7 and MDA-MB-231. Moreover, they were predicted to have low toxicity towards normal cell lines. Secondly, approximately 242 BC-related molecular targets were collected from various databases and used to construct a protein–protein interaction (PPI) network, which revealed the most important molecular targets and signaling pathways in the pathogenesis of BC. All the identified compounds in the extract were then subjected to inverse docking against all proteins hosted in the Protein Data bank (PDB) to discover the BC-related proteins that these compounds can target. Approximately, 10.74% of the collected BC-related proteins were potential targets for 70% of the compounds identified in CE. Further validation of the docking results using molecular dynamic simulations (MDS) and binding free energy calculations revealed that only 2.47% of the collected BC-related proteins could be targeted by 30% of the CE-derived compounds. According to docking and MDS experiments, protein-pathway and compound-protein interaction networks were constructed to determine the signaling pathways that the CE compounds could influence. This paper highlights the potential of marine natural products as effective anticancer agents and reports the discovery of novel anti-breast cancer AgNPs.

show abstract

Targeting allosteric sites of human aromatase: a comprehensive in-silico and in-vitro workflow to find potential plant-based anti-breast cancer therapeutics

Cited by 12 publications

References 47 publications

Antiproliferative potential of Physalis peruviana-derived magnolin against pancreatic cancer: a comprehensive in vitro and in silico study

Antiproliferative potential of Physalis peruviana-derived magnolin against pancreatic cancer: a comprehensive in vitro and in silico study

In Silico-Based Discovery of Natural Anthraquinones with Potential against Multidrug-Resistant E. coli

Anticancer Potential of Green Synthesized Silver Nanoparticles of the Soft Coral Cladiella pachyclados Supported by Network Pharmacology and In Silico Analyses

Contact Info

Product

Resources

About