Binary and Ternary Complexes of Arteether β-CD - Characterization, Molecular Modeling and in Vivo Studies

Aim: The aim of this study was to simultaneously enhance the solubility and stability of bacogenins by a ternary system comprised of hydrogenated soy lecithin and a third auxiliary substance, fulvic acid. Method: Both ternary and binary complexes were prepared using the solvent evaporation method and prepared binary and ternary systems were characterized by Fourier transform infrared technique, differential scanning calorimeter and scanning electron microscope. The entrapment efficacy in both binary and ternary system was calculated and the effect on the solubility, dissolution and stability of bacogenins (hydrolyzed bacoside rich extract) in 40% ethanol was found out. Furthermore, the prepared formulations were subjected to behavioural pharmacological studies. Results : FTIR, DSC, and SEM studies in totality confirmed the formation of binary and ternary complexes. Enhancement in solubility was observed, and the order of releasecharacteristics was found to be BHFS> BHSL>BHF> BH when the dissolution studies were carried out in 40% aqueous solution of ethanol. A significant improvement in the memory and antioxidant capacity was noticed in both binary, ternary complexes and fulvic acid treatment groups. Conclusion: The results revealed that the ternary complex could be a promising drug delivery system to improve the oral bioavailability of the bacogenins.

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N,N′-Ethylene-di-l-Cysteine (EC) complexes of Ga(III) and In(III): Molecular modeling, thermodynamic stability and in vivo studies

Nuclear Medicine and Biology ◽

10.1016/0969-8051(94)00106-t ◽

1995 ◽

Vol 22 (2) ◽

pp. 165-173 ◽

Cited By ~ 28

Author(s):

Carolyn J. Anderson ◽

Christy S. John ◽

Yuejin J. Li ◽

Robert D. Hancock ◽

Timothy J. Mccarthy ◽

...

Keyword(s):

Molecular Modeling ◽

Thermodynamic Stability ◽

In Vivo Studies

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Design, synthesis, molecular modeling, in vivo studies and anticancer evaluation of quinazolin-4(3H)-one derivatives as potential VEGFR-2 inhibitors and apoptosis inducers

Bioorganic Chemistry ◽

10.1016/j.bioorg.2019.103422 ◽

2020 ◽

Vol 94 ◽

pp. 103422 ◽

Cited By ~ 15

Author(s):

Hazem A. Mahdy ◽

Mohammed K. Ibrahim ◽

Ahmed M. Metwaly ◽

Amany Belal ◽

Ahmed B.M. Mehany ◽

...

Keyword(s):

Molecular Modeling ◽

In Vivo Studies ◽

Design Synthesis

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Hydrophobically modified polyethylenimine-based ternary complexes for targeting brain tumor: stability, in vitro and in vivo studies

Artificial Cells Nanomedicine and Biotechnology ◽

10.1080/21691401.2017.1282497 ◽

2017 ◽

Vol 45 (8) ◽

pp. 1685-1698 ◽

Cited By ~ 3

Author(s):

Brahmanand Dube ◽

Abhijeet Pandey ◽

Ganesh Joshi ◽

Krutika Sawant

Keyword(s):

Brain Tumor ◽

Ternary Complexes ◽

In Vivo Studies ◽

Hydrophobically Modified

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Synthesis, in vitro and in vivo studies, and molecular modeling of N-alkylated dextromethorphan derivatives as non-competitive inhibitors of α3β4 nicotinic acetylcholine receptor

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2014.10.036 ◽

2014 ◽

Vol 22 (24) ◽

pp. 6846-6856 ◽

Cited By ~ 4

Author(s):

Krzysztof Jozwiak ◽

Katarzyna M. Targowska-Duda ◽

Agnieszka A. Kaczor ◽

Joanna Kozak ◽

Agnieszka Ligeza ◽

...

Keyword(s):

Molecular Modeling ◽

Acetylcholine Receptor ◽

Nicotinic Acetylcholine Receptor ◽

In Vivo Studies ◽

Nicotinic Acetylcholine ◽

Competitive Inhibitors

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Design, synthesis, molecular modeling, in vivo studies and anticancer activity evaluation of new phthalazine derivatives as potential DNA intercalators and topoisomerase II inhibitors

Bioorganic Chemistry ◽

10.1016/j.bioorg.2020.104233 ◽

2020 ◽

Vol 103 ◽

pp. 104233 ◽

Cited By ~ 1

Author(s):

Abdel-Ghany A. El-Helby ◽

Helmy Sakr ◽

Rezk R. Ayyad ◽

Hazem A. Mahdy ◽

Mohamed M. Khalifa ◽

...

Keyword(s):

Molecular Modeling ◽

Anticancer Activity ◽

Topoisomerase Ii ◽

In Vivo Studies ◽

Design Synthesis ◽

Dna Intercalators ◽

Topoisomerase Ii Inhibitors ◽

Activity Evaluation

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Co-Inhibition of P-gp and Hsp90 by an Isatin-Derived Compound Contributes to the Increase of the Chemosensitivity of MCF7/ADR-Resistant Cells to Doxorubicin

Molecules ◽

10.3390/molecules27010090 ◽

2021 ◽

Vol 27 (1) ◽

pp. 90

Author(s):

Ashraf N. Abdalla ◽

Miriana Di Stefano ◽

Giulio Poli ◽

Tiziano Tuccinardi ◽

Ammar Bader ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Modeling ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Efflux Pump ◽

Binding Mode ◽

Inhibitory Effect ◽

In Vivo Studies ◽

Mcf7 Cells

Breast cancer is a complex and multi-drug resistant (MDR) disease, which could result in the failure of many chemotherapeutic clinical agents. Discovering effective molecules from natural products or by derivatization from known compounds is the interest of many research studies. The first objective of the present study is to investigate the cytotoxic combinatorial, chemosensitizing, and apoptotic effects of an isatin derived compound (5,5-diphenylimidazolidine-2,4-dione conjugated with 5-substituted isatin, named HAA2021 in the present study) against breast cancer cells (MCF7) and breast cancer cells resistant to doxorubicin (MCF7/ADR) when combined with doxorubicin. The second objective is to investigate the binding mode of HAA2021 withP-glycoprotein (P-gp) and heat shock protein 90 (Hsp90), and to determine whether their co-inhibition by HAA2021 contribute to the increase of the chemosensitization of MCF7/ADR cells to doxorubicin. The combination of HAA2021, at non-toxic doses, with doxorubicin synergistically inhibited the proliferation while inducing significant apoptosis in MCF7 cells. Moreover, HAA2021 increased the chemosensitization of MCF7/ADR cells to doxorubicin, resulting in increased cytotoxicity/selectivity and apoptosis-inducing efficiency compared with the effect of doxorubicin or HAA2021 alone against MCF7/ADR cells. Molecular modeling showed that two molecules of HAA2021 bind to P-gp at the same time, causing P-gp inhibitory effect of the MDR efflux pump, and accumulation of Rhodamine-123 (Rho123) in MCF7/ADR cells. Furthermore, HAA2021 stably interacted with Hsp90α more efficiently compared with 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), which was confirmed with the surface plasmon resonance (SPR) and molecular modeling studies. Additionally, HAA2021 showed multi-target effects via the inhibition of Hsp90 and nuclear factor kappa B (NF-𝜅B) proteins in MCF7 and MCF7/ADR cells. Results of real time-PCR also confirmed the synergistic co-inhibition of P-gp/Hsp90α genes in MCF7/ADR cells. Further pharmacokinetic and in vivo studies are warranted for HAA2021 to confirm its anticancer capabilities.

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