Microwave-Assisted Facile Synthesis, Anticancer Evaluation and Docking Study of N-((5-(Substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) Benzamide Derivatives
Abstract
:1. Introduction
2. Result and Discussion
2.1. Chemistry
2.2. In Vitro Anticancer Activity
2.3. Molecular Docking
2.4. In Silico ADMET Prediction
3. Materials and Methods
3.1. General Information
3.1.1. Step I: General Process for Synthesis of 2-Benzamidoacetic Acid [34]
3.1.2. Step II: General Procedure for Synthesis of N-((5-Amino-1,3,4-thiadiazol-2-yl)methyl) Benzamide [35]
3.1.3. Step III: General procedure for synthesis of (E)-N-((5-(substituted methyleneamino)-1,3,4-thiadiazol-2-yl)methyl) benzamide 7(a–l)
3.2. In Vitro Anticancer Screening
Experimental procedure for MTT assay
3.3. Computational Study
Molecular Docking and In Silico ADMET Prediction
4. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
Entry | Conventional Method | Microwave Method | ||||
---|---|---|---|---|---|---|
Solvent | Temperature °C | Time (h) | Yield (%) | Time (min) | Yield (%) | |
7a | Ethanol | 80–90 | 3.30 | 78 | 8 | 95 |
7b | Ethanol | 80–90 | 5.10 | 77 | 12 | 92 |
7c | Ethanol | 80–90 | 5.00 | 78 | 12 | 94 |
7d | Ethanol | 80–90 | 7.20 | 66 | 15 | 94 |
7e | Ethanol | 80–90 | 7.25 | 52 | 15 | 92 |
7f | Ethanol | 80–90 | 8.00 | 48 | 18 | 92 |
7g | Ethanol | 80–90 | 5.25 | 76 | 12 | 95 |
7h | Ethanol | 80–90 | 7.30 | 66 | 15 | 88 |
7i | Ethanol | 80–90 | 8.00 | 68 | 20 | 86 |
7j | Ethanol | 80–90 | 8.00 | 48 | 20 | 88 |
7k | Ethanol | 80–90 | 4.15 | 44 | 10 | 85 |
7l | Ethanol | 80–90 | 4.25 | 56 | 10 | 84 |
Entry | GI50 µM | ||||
---|---|---|---|---|---|
MCF-7 | HeLa | SKMEL-2 | HL-60 | MCF-10A | |
7a | 22.9 | 32.8 | 21.9 | 21.7 | >100 |
7b | 28.7 | 39.0 | 22.9 | 28.2 | 86.1 |
7c | 32.4 | 41.1 | 27.5 | 33.3 | ND |
7d | 36.7 | 52.4 | 34.0 | 40.2 | ND |
7e | 35.2 | 46.8 | 28.1 | 39.6 | ND |
7f | 38.4 | 49.2 | 30.0 | 37.5 | ND |
7g | 41.0 | 66.1 | 46.4 | 42.4 | ND |
7h | 46.2 | 71.7 | 49.1 | 48.2 | ND |
7i | 49.0 | 78.0 | 52.6 | 45.8 | ND |
7j | 51.4 | 78.8 | 55.7 | 49.9 | ND |
7k | 11.7 | 23.8 | 19.6 | 35.5 | > 100 |
7l | 19.0 | 28.8 | 22.0 | 29.9 | > 100 |
ADR | < 10 | < 10 | < 10 | < 10 | ND |
Compound | Docking Score | Compound | Docking Score |
---|---|---|---|
7a | −6.61 | 7h | −6.33 |
7b | −6.56 | 7i | −6.61 |
7c | −5.93 | 7j | −5.10 |
7d | −5.82 | 7k | −7.56 |
7e | −5.84 | 7l | −7.32 |
7f | −5.66 | ADR | −4.33 |
7g | −5.26 |
Entry | M.W a | LogP o/w b (−2.0–6.5) | n-ON c (<10) | n-OHNH d (<5) | PSA e (7–200) | log Khsa f (−1.5–1.2) | Log S g (−6–0.5) | % ABS h | #Meta i (1–8) | Log HERG j Below−5 | Lipinski Rule of 5 (≤1) |
---|---|---|---|---|---|---|---|---|---|---|---|
7a | 356.8 | 4.82 | 5.5 | 1 | 76.2 | 0.31 | −5.8 | 98 | 2 | −6.8 | 0 |
7b | 391.2 | 5.34 | 5.5 | 1 | 74.4 | 0.37 | −6.1 | 99 | 2 | −6.6 | 0 |
7c | 338.3 | 5.18 | 6.2 | 2 | 98.4 | 0.02 | −4.7 | 89 | 3 | −6.7 | 0 |
7d | 338.3 | 5.17 | 6 | 2 | 98.2 | 0.03 | −4.3 | 88 | 3 | −6.5 | 0 |
7e | 368.4 | 5.27 | 7.2 | 1 | 133.3 | −0.04 | −4.7 | 75 | 3 | −6.6 | 0 |
7f | 382.4 | 5.09 | 7 | 2 | 105.7 | 0.16 | −5.5 | 91 | 4 | −6.9 | 0 |
7g | 352.4 | 4.91 | 6.2 | 1 | 83.9 | 0.16 | −5.1 | 100 | 3 | −6.7 | 0 |
7h | 382.4 | 5.20 | 7 | 1 | 89.0 | 0.19 | −5.4 | 100 | 4 | −6.7 | 0 |
7i | 412.2 | 4.05 | 7.7 | 1 | 95.4 | 0.17 | −5.4 | 100 | 5 | −6.5 | 0 |
7j | 412.2 | 4.08 | 7.7 | 1 | 97.6 | 0.19 | −5.6 | 100 | 5 | −6.6 | 0 |
7k | 312.3 | 3.91 | 6 | 1 | 84.7 | −0.11 | −4.0 | 94 | 3 | −6.3 | 0 |
7l | 328.4 | 4.11 | 5 | 1 | 85.6 | −0.21 | −4.2 | 95 | 3 | −6.2 | 0 |
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Tiwari, S.V.; Siddiqui, S.; Seijas, J.A.; Vazquez-Tato, M.P.; Sarkate, A.P.; Lokwani, D.K.; Nikalje, A.P.G. Microwave-Assisted Facile Synthesis, Anticancer Evaluation and Docking Study of N-((5-(Substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) Benzamide Derivatives. Molecules 2017, 22, 995. https://doi.org/10.3390/molecules22060995
Tiwari SV, Siddiqui S, Seijas JA, Vazquez-Tato MP, Sarkate AP, Lokwani DK, Nikalje APG. Microwave-Assisted Facile Synthesis, Anticancer Evaluation and Docking Study of N-((5-(Substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) Benzamide Derivatives. Molecules. 2017; 22(6):995. https://doi.org/10.3390/molecules22060995
Chicago/Turabian StyleTiwari, Shailee V., Sumaiya Siddiqui, Julio A. Seijas, M. Pilar Vazquez-Tato, Aniket P. Sarkate, Deepak K. Lokwani, and Anna Pratima G. Nikalje. 2017. "Microwave-Assisted Facile Synthesis, Anticancer Evaluation and Docking Study of N-((5-(Substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) Benzamide Derivatives" Molecules 22, no. 6: 995. https://doi.org/10.3390/molecules22060995
APA StyleTiwari, S. V., Siddiqui, S., Seijas, J. A., Vazquez-Tato, M. P., Sarkate, A. P., Lokwani, D. K., & Nikalje, A. P. G. (2017). Microwave-Assisted Facile Synthesis, Anticancer Evaluation and Docking Study of N-((5-(Substituted methylene amino)-1,3,4-thiadiazol-2-yl)methyl) Benzamide Derivatives. Molecules, 22(6), 995. https://doi.org/10.3390/molecules22060995