Synthesis of Novel Potent Biologically Active N-Benzylisatin-Aryl Hydrazones in Comparison with Lung Cancer Drug ‘Gefitinib’
Abstract
:Featured Application
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals and Solvents Were of Commercial Reagent Grade (Sigma-Aldrich, St. Louis, MO, USA) and Used without Further Purification
2.2. Preparation and Characterization of Target Compounds
2.2.1. 1-Benzylindoline-2,3-dione (3)
2.2.2. (Z)-1-Benzyl-3-hydrazonoindolin-2-one (4)
2.2.3. General Procedure for the Synthesis of 6a–j
1-Benzyl-3-((4-(dimethylamino) benzylidene)hydrazono)indolin-2-one (6a)
1-Benzyl-3-(((4-chlorocyclohexa−1, 5-dien-1-yl) methylene)hydrazono)indolin-2-one (6b)
1-Benzyl-3-((4-hydroxybenzylidene)hydrazono)indolin-2-one (6c)
1-Benzyl-3-((2-bromobenzylidene)hydrazono)indolin-2-one (6d)
1-Benzyl-3-((E)-(3-bromobenzylidene)hydrazono)indolin-2-one (6e)
1-Benzyl-3-((4-bromobenzylidene)hydrazono)indolin-2-one (6f)
1-Benzyl-3-((2-methyl benzylidene)hydrazono)indolin-2-one (6g)
1-Benzyl-3-((3-methylbenzylidene)hydrazono)indolin-2-one (6h)
1-Benzyl-3-((4-methylbenzylidene)hydrazono)indolin-2-one (6i)
1-Benzyl-3-((4-(methylthio)benzylidene)hydrazono)indolin-2-one (6j)
2.3. Antimicrobial Evaluation
2.4. Antiproliferative Assay
2.5. In Silico ADME Prediction Analysis
3. Results and Discussion
3.1. Synthesis of 6a–j
3.2. Biological Evaluation
3.2.1. Antimicrobial Evaluation of 6a–j
3.2.2. Antiproliferative Activity of 6a–j
3.3. Structure Activity Relationships (SARs) of 6a–j
3.4. In Silico Drug Likeness Property Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Compound | | IC50 ( µM) | |
---|---|---|---|
A549 | Hela | ||
4 | – | 14 ± 2.15 | 46 ± 1.30 |
6a | 4-N(CH3)2 | 23.7 ± 0.69 | 25.1 ± 0.95 |
6b | 4-Cl | 22 ± 1.11 | 14.8 ± 0.94 |
6c | 4-OH | 4.35 ± 0.05 | 4 ± 0.09 |
6d | 2-Br | 7.3 ± 0.52 | 6.7 ± 0.17 |
6e | 3-Br | 41 ± 1.20 | 9.1 ± 0.35 |
6f | 4-Br | 7.30 ± 0.03 | 7.4 ± 0.20 |
6g | 2-CH3 | 7.5 ± 0.11 | 7.7 ± 0.21 |
6h | 3-CH3 | 8.4 ± 0.25 | 13.4 ± 0.35 |
6i | 4-CH3 | 17 ± 0.70 | 18.5 ± 0.65 |
6j | 4-SCH3 | 14.6 ± 0.53 | 9 ± 0.86 |
Gefitinib | – | 15.2 ± 0.48 | 7.3 ± 0.42 |
No. | MW b | HBD c | HBA d | logPo/w e | logS f | logP | HERGg | Caco-2 h | BBB i | MDCKj | HOA(%) k |
---|---|---|---|---|---|---|---|---|---|---|---|
6a | 382 | 0 | 6.5 | 4.77 | −5.76 | 10.2 | −7.35 | 3189 | −0.36 | 1733.1 | 100 |
6b | 374 | 0 | 5.5 | 4.86 | −5.60 | 9.4 | −7.16 | 3720 | −0.02 | 5054.6 | 100 |
6c | 355 | 1 | 6.25 | 3.82 | −5.07 | 11.8 | −7.13 | 1102 | −0.83 | 549.7 | 100 |
6d | 418 | 0 | 5.5 | 4.87 | −5.58 | 9.5 | −7.19 | 3656 | −0.04 | 4745.7 | 100 |
6e | 418 | 0 | 5.5 | 4.93 | −5.74 | 9.4 | −7.20 | 3637 | −0.02 | 5296.9 | 100 |
6f | 418 | 0 | 5.5 | 4.93 | −5.72 | 9.4 | −7.19 | 3719 | −0.01 | 5433.8 | 100 |
6 g | 353 | 0 | 5.5 | 4.61 | −5.30 | 9.4 | −7.14 | 3754 | −0.19 | 2067.3 | 100 |
6 h | 353 | 0 | 5.5 | 4.67 | −5.46 | 9.4 | −7.17 | 3638 | −0.21 | 1998.3 | 100 |
6i | 353 | 0 | 5.5 | 4.67 | −5.44 | 9.3 | −7.16 | 3734 | −0.20 | 2054.9 | 100 |
6j | 385 | 0 | 6.0 | 5.01 | −5.93 | 9.7 | −7.38 | 3479 | −0.21 | 3246.6 | 100 |
Gl | 447 | 1 | 7.7 | 4.37 | −5.23 | 10.8 | −7.12 | 1053 | 0.31 | 2313.1 | 100 |
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Al-Salem, H.S.; Abuelizz, H.A.; Issa, I.S.; Mahmoud, A.Z.; AlHoshani, A.; Arifuzzaman, M.; Rahman, A.F.M.M. Synthesis of Novel Potent Biologically Active N-Benzylisatin-Aryl Hydrazones in Comparison with Lung Cancer Drug ‘Gefitinib’. Appl. Sci. 2020, 10, 3669. https://doi.org/10.3390/app10113669
Al-Salem HS, Abuelizz HA, Issa IS, Mahmoud AZ, AlHoshani A, Arifuzzaman M, Rahman AFMM. Synthesis of Novel Potent Biologically Active N-Benzylisatin-Aryl Hydrazones in Comparison with Lung Cancer Drug ‘Gefitinib’. Applied Sciences. 2020; 10(11):3669. https://doi.org/10.3390/app10113669
Chicago/Turabian StyleAl-Salem, Huda S., Hatem A. Abuelizz, Iman S. Issa, Amany Z. Mahmoud, Ali AlHoshani, Md Arifuzzaman, and A. F. M. Motiur Rahman. 2020. "Synthesis of Novel Potent Biologically Active N-Benzylisatin-Aryl Hydrazones in Comparison with Lung Cancer Drug ‘Gefitinib’" Applied Sciences 10, no. 11: 3669. https://doi.org/10.3390/app10113669
APA StyleAl-Salem, H. S., Abuelizz, H. A., Issa, I. S., Mahmoud, A. Z., AlHoshani, A., Arifuzzaman, M., & Rahman, A. F. M. M. (2020). Synthesis of Novel Potent Biologically Active N-Benzylisatin-Aryl Hydrazones in Comparison with Lung Cancer Drug ‘Gefitinib’. Applied Sciences, 10(11), 3669. https://doi.org/10.3390/app10113669