The Synthesis, Characterization, Molecular Docking and In Vitro Antitumor Activity of Benzothiazole Aniline (BTA) Conjugated Metal-Salen Complexes as Non-Platinum Chemotherapeutic Agents
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis and Characterization
2.2. Complex Stability
2.3. Antiproliferative Activity
2.4. Intracellular ROS Generation
2.5. Ligand Docking Simulation of L, MnL, and BTA
3. Materials and Methods
3.1. Reagents and Instruments
3.2. Synthesis and Characterization of Ligand
N-(4-Benzothiazol-2-yl-phenyl)-2,3-bis-[(2-hydroxy-benzylidene)-amino]-propionamide (L)
3.3. Synthesis and Characterization of Metal Complexes
3.3.1. Synthesis of MnL
3.3.2. Synthesis of FeL
3.3.3. Synthesis of CoL
3.3.4. Synthesis of NiL
3.3.5. Synthesis of CuL
3.3.6. Synthesis of ZnL
3.4. Stability of the Lead Complex
3.5. Cell Culture
3.6. Cell Viability Assay
3.7. Intracellular ROS Analysis
3.8. Computational Method for Predicting Ligand-DNA Complexes
3.9. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compounds | IC50 (μM) | Selectivity Index (SI) a | |||
---|---|---|---|---|---|
Human Liver Cancer (HepG2) | Human Colon Cancer (HT-29) | Human Breast Cancer (MCF-7) | Mouse Liver Hepatocyte (AML-12) | ||
L | 14.2 ± 7.0 | 135.0 ± 4.4 | 98.1 ± 7.9 | >300 | 21.13 |
MnL | 5.8 ± 0.3 | 15.1 ± 1.1 | 34.5 ± 4.0 | 9.4 ± 0.8 | 1.62 |
FeL | 41.2 ± 3.8 | 110.3 ± 17.6 | 142.0 ± 8.9 | 48.1 ± 0.7 | 1.17 |
CoL | 32.1 ± 4.4 | 181.8 ± 16.4 | 146.5 ± 30.5 | 14.7 ± 0.5 | 0.46 |
NiL | 193.6 ± 17.7 | 167.1 ± 5.8 | >300 | 12.4 ± 0.6 | 0.06 |
CuL | 55.5 ± 0.6 | 135.1 ± 10.0 | 271.2 ± 37.0 | 46.5 ± 0.8 | 0.84 |
ZnL | 17.6 ± 0.4 | 254.8 ± 33.8 | 57.6 ± 5.8 | 52.6 ± 0.5 | 2.99 |
Cisplatin b | 54.2 ± 31.8 | 39.1 ± 0.6 | 203.8 ± 27.3 | 32.1 ± 4.4 | 0.59 |
BTA b | 52.0 ± 5.7 | 275.3 ± 5.0 | 103.9 ± 28.6 | >300 | 5.77 |
Compounds | Docking Binding Energy (kcal/mol) | ||
---|---|---|---|
1BNA a | 1LU5 b | 3CO3 c | |
L | −7.239 | −6.307 | −7.718 |
MnL | −5.894 | −4.253 | −3.340 |
BTA | −6.618 | −4.259 | −5.941 |
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Islam, M.K.; Ha, S.; Baek, A.-R.; Yang, B.-W.; Kim, Y.-H.; Park, H.-J.; Kim, M.; Nam, S.-W.; Lee, G.-H.; Chang, Y. The Synthesis, Characterization, Molecular Docking and In Vitro Antitumor Activity of Benzothiazole Aniline (BTA) Conjugated Metal-Salen Complexes as Non-Platinum Chemotherapeutic Agents. Pharmaceuticals 2022, 15, 751. https://doi.org/10.3390/ph15060751
Islam MK, Ha S, Baek A-R, Yang B-W, Kim Y-H, Park H-J, Kim M, Nam S-W, Lee G-H, Chang Y. The Synthesis, Characterization, Molecular Docking and In Vitro Antitumor Activity of Benzothiazole Aniline (BTA) Conjugated Metal-Salen Complexes as Non-Platinum Chemotherapeutic Agents. Pharmaceuticals. 2022; 15(6):751. https://doi.org/10.3390/ph15060751
Chicago/Turabian StyleIslam, Md. Kamrul, Seongmin Ha, Ah-Rum Baek, Byeong-Woo Yang, Yeoun-Hee Kim, Hyun-Jin Park, Minsup Kim, Sung-Wook Nam, Gang-Ho Lee, and Yongmin Chang. 2022. "The Synthesis, Characterization, Molecular Docking and In Vitro Antitumor Activity of Benzothiazole Aniline (BTA) Conjugated Metal-Salen Complexes as Non-Platinum Chemotherapeutic Agents" Pharmaceuticals 15, no. 6: 751. https://doi.org/10.3390/ph15060751