- Novel benzo[4,5]thiazolo[2,3-C][1,2,4]triazoles: Design, synthesis, anticancer evaluation, kinase profiling and molecular docking study
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In the current study, we report the synthesis and cytotoxic evaluation of a new series of S-benzo[4,5]thiazolo[2,3-c][1,2,4]triazole-based derivatives 8-12. Cytotoxicity of the new compounds was investigated in A549, MCF-7, and Hep3B cancer cell lines. Among these derivatives, compound 12 bearing an isatin moiety was the most active derivative (IC50 = 2.40-3.53 μM). A mechanistic study of compound 12 was performed using the kinase profiling test to explore its inhibitory activity against 10 types of the oncogenic kinases and the potential activation of caspase 3/7 enzymes. The results revealed that compound 12 showed moderate inhibition of the EGFR and LCK kinases. Moreover, compound 12 also activated caspase-3/7 in A549 cells. The docking study of compound 12 into EGFR ATP-active site revealed that it fits nicely with good binding affinity. Together, the results indicated that compound 12 could serve as a good lead for developing new potential anticancer agents.
- Abdelazeem, Ahmed H.,Alqahtani, Alaa M.,Arab, Hany H.,Gouda, Ahmed M.,Safi El-Din, Asmaa G.
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- Synthesis, biological evaluation and kinase profiling of novel S-benzo[4,5]thiazolo[2,3-c][1,2,4]triazole derivatives as cytotoxic agents with apoptosis-inducing activity
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A novel set of S-benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles was synthesized. Cytotoxicity of these compounds was evaluated against three cancer cell lines of different origins, Hep3B, A549, and MCF-7. Three of these compounds were screened by NCI for growth inhibitory activities against 60 cancer cell lines. The results revealed significant cytotoxic activities for compounds 13a-i. Among these derivatives, compounds 13c and 13f-13i exhibited the highest cytotoxicity against the selected cancer cell lines with IC50 values between 3.17 and 14.18 μM. The structure-activity relationship of compounds 13a-i indicated favorable cytotoxic results on the expansion of the cyclic amine and the substitution with aminothiazole moiety. A mechanistic study revealed the activation of caspase-3/7 in A549 cells on treatment with compounds 13f-i at 5–20 μM. Moreover, the results of flow cytometric analysis suggested that compound 13i efficiently induced apoptosis in a dose-dependent manner. Compounds 13f,g,i also exhibited a weak to moderate inhibition of multiple kinases where compound 13i was the most active in inhibiting the activity of CDK2/Cyclin A1 (IC50 = 4.65 μM). The current work provided a novel set of compounds with cytotoxic, kinase inhibition, and apoptosis-inducing activities, which can serve as a lead for further optimization.
- Abdelazeem, Ahmed H.,Alqahtani, Alaa M.,Bukhari, Syed Nasir Abbas,Gouda, Ahmed M.,Omar, Hany A.
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- Design, synthesis and biological evaluation of novel benzo[4,5]thiazolo[2,3-c][1,2,4]triazole derivatives as potential anticancer agents
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In the present study, we have designed and synthesized a novel series of benzothiazolotriazole derivatives as potential anticancer agents. The anticancer activity of the newly synthesized compounds was evaluated against three cancerous cell lines; A549 (human lung adenocarcinoma), MCF-7 (human breast carcinoma) and Hep3B (human hepatocellular carcinoma) using MTT assay. Among this series, compounds 15 and 16 showed the most promising anticancer activity with IC50 values between 11.1 to 21.5 μM. Kinase profiling was performed for the most potent compounds 15 and 16 and it revealed weak inhibitory activity against 10 various kinases, where the highest inhibition was against CDK2/Cyclin A1 by compound 15. Furthermore, caspase-3/7 assay also indicated that the same compound 15 has the ability to induce apoptosis through the activation of effector caspase-3/7 family. Therefore, it could be deduced that the S-benzo[4,5]thiazolo[2,3-c][1,2,4]triazole is a promising novel anticancer scaffold with antiproliferative and apoptosis-inducing activities deserves to be taken up as a lead for further structural optimization.
- Abdelazeem, Ahmed H.,Gouda, Ahmed M.,Omar, Hany A.,Alrobaian, Majed
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p. 625 - 636
(2018/08/03)
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- Synthesis and antifungal activity of some s-mercaptotriazolobenzothiazolyl amino acid derivatives
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A series of s-triazolobenzothiazolylthioacetyl/propionyl amino acid derivatives were synthesized with the aim of evaluating their antifungal activity. Their chemical structures were confirmed by 1H, 13C NMR, IR, mass spectrometry and elemental analyses. The synthesized derivatives were screened for their antifungal activity against Aspergillus flavus and Candida albicans. Five compounds (3, 5, 7c, 8 and 17) were found to possess high activity comparable to fluconazole at 100 μg/mL against C. albicans.
- Aboelmagd,Ali, Ibrahim A.I.,Salem, Ezzeldin M.S.,Abdel-Razik
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p. 503 - 511
(2013/04/10)
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- Synthesis of new triazolo and pyrazolo benzothiazoles
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Benzothiazole-2-thiol 1 on heating with excess of hydrazine hydrate yields 2-hydrazino-1,3-benzothiazole (2). Compound 2 on reaction with carbon disulfide in alkaline medium affords [1,2,4] triazolo [3,4-b] [1,3] benzothiazole-3-thiol (3). Condensation of 2 with various substituted aryl aldehydes yields corresponding hydrazine derivatives (4), which on cyclisation with acetic anhydride gave corresponding [1,2,4] triazolo [3,4-6] [1,3] benzothiazoles (5). Some other triazolo derivatives (6,7,8) of benzothiazole were obtained by the cyclization of 2 with benzoyl chloride, acetyl chloride and formic acid respectively. Again compound 2 on condensation with acetyl acetone and ethylacetoacetate gives pyrazolo derivatives (9,10) respectively. The synthesized compounds were characterized by elemental and spectral analysis.
- Deshmukh,Patil,Jadhav,Shejwal
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p. 163 - 166
(2013/09/23)
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- Agent for the control of plant-pathogenic organisms
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Methods employing and compositions comprising, for the control of plant-pathogenic organisms, specified triazolobenzoxazole and triazolobenzothiazole compounds; and novel methods for the preparation of the compounds.
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