Dataset Information

Indole-fused benzooxazepines: a new structural class of anticancer agents.

ABSTRACT:

Aim

A new series of compounds (1a-16a) bearing indole-fused benzooxazepine was synthesized, characterized and evaluated for anticancer activity.

Materials & methods

In this study, all the synthesized compounds were screened via in vitro anticancer testing on Hep-G2 cancer cell line. A computational study was carried out on cancer-related targets including IL-2, IL-6, COX-2 Caspase-3 and Caspase-8.

Results

Some of the synthesized compounds effectively controlled the growth of cancerous cells.

Conclusion

The most active compounds - 6a, 10a, 13a, 14a and 15a - exemplify notable anticancer profile with GI₅₀ <10 μg/ml. Preliminary structure-activity relationship among the tested compounds can produce an assumption that the electronegative groups at phenyl ring attached with indole-fused benzooxazepine are instrumental for the activity. Molecular docking study showed crucial hydrogen bond and π-π stacking interactions, with good ADMET profiling and molecular dynamic simulation.

SUBMITTER: Singh AK

PROVIDER: S-EPMC5351710 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Indole-fused benzooxazepines: a new structural class of anticancer agents.

Singh Ashok K AK Singh Ashok K AK Raj Vinit V Rai Amit A Keshari Amit K AK Saha Sudipta S

Future science OA 20170104 1

<h4>Aim</h4>A new series of compounds (<b>1a-16a</b>) bearing indole-fused benzooxazepine was synthesized, characterized and evaluated for anticancer activity.<h4>Materials & methods</h4>In this study, all the synthesized compounds were screened via <i>in vitro</i> anticancer testing on Hep-G2 cancer cell line. A computational study was carried out on cancer-related targets including IL-2, IL-6, COX-2 Caspase-3 and Caspase-8.<h4>Results</h4>Some of the synthesized compounds effectively controlle ...[more]

PMID: 28344831

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Project description:The development of new approaches for the synthesis of new bioactive heterocyclic derivatives is of the utmost importance for pharmaceutical industry. In this regard, the present study reports the green synthesis of new benzaldazine and ketazine derivatives via the condensation of various carbonyl compounds (aldehydes and ketones with the 3-(1-hydrazineylideneethyl)-1H-indole using the grinding method with one drop of acetic acid). Various spectroscopic techniques were used to identify the structures of the synthesized derivatives. Furthermore, the anticancer activities of the reported azine derivatives were evaluated against colon, hepatocellular, and breast carcinoma cell lines using the MTT technique with doxorubicin as a reference medication. The findings suggested that the synthesized derivatives exhibited potential anti-tumor activities toward different cell lines. For example, 3c, 3d, 3h, 9, and 13 exhibited interesting activity with an IC50 value of 4.27-8.15 µM towards the HCT-116 cell line as compared to doxorubicin (IC50 = 5.23 ± 0.29 µM). In addition, 3c, 3d, 3h, 9, 11, and 13 showed excellent cytotoxic activities (IC50 = 4.09-9.05 µM) towards the HePG-2 cell line compared to doxorubicin (IC50 = 4.50 ± 0.20 µM), and 3d, 3h, 9, and 13 demonstrated high potency (IC50 = 6.19-8.39 µM) towards the breast cell line (MCF-7) as compared to the reference drug (IC50 = 4.17 ± 0.20 µM). The molecular interactions between derivatives 3a-h, 7, 9, 11, 13, and the CDK-5 enzyme (PDB ID: 3IG7) were studied further using molecular docking indicating a high level of support for the experimental results. Furthermore, the drug-likeness analysis of the reported derivatives indicated that derivative 9 (binding affinity = -8.34 kcal/mol) would have a better pharmacokinetics, drug-likeness, and oral bioavailability as compared to doxorubicin (-7.04 kcal/mol). These results along with the structure-activity relationship (SAR) of the reported derivatives will pave the way for the design of additional azines bearing indole with potential anticancer activities.

Dataset Information

Indole-fused benzooxazepines: a new structural class of anticancer agents.

Aim

Materials & methods

Results

Conclusion

Publications

Indole-fused benzooxazepines: a new structural class of anticancer agents.

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