Design and synthesis of substituted (1-(benzyl)-1H-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone conjugates : study on their apoptosis inducing ability and tubulin polymerization inhibition
This journal is © The Royal Society of Chemistry..
A library of substituted (1-(benzyl)-1H-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone derivatives were designed, synthesized and screened for their in vitro cytotoxic activity against BT-474, HeLa, MCF-7, NCI-H460 and HaCaT cells by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized analogues, compound 10ec displayed the highest cytotoxicity with the IC50 value of 0.99 ± 0.01 μM towards BT-474 cancer cell line. The target compound (10ec) was also evaluated for its tubulin polymerization inhibition study. Detailed biological studies such as acridine orange/ethidium bromide (AO/EB), DAPI and annexin V-FITC/propidium iodide staining assay suggested that compound 10ec induced the apoptosis of BT-474 cells. The clonogenic assay revealed that the inhibition of colony formation in BT-474 cells by 10ec in concentration-dependent manner. Moreover, the flow cytometric analysis revealed that 10ec induced apoptosis via cell cycle arrest at the sub-G1 and G2/M phase. In silico studies of sulfonyl piperazine-integrated triazole conjugates unveil that they possess drug-like properties. According to the molecular modelling studies, compound 10ec binds to the colchicine binding site of the tubulin.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
RSC medicinal chemistry - 11(2020), 11 vom: 18. Nov., Seite 1295-1302 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Manasa, Kesari Lakshmi [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 02.04.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1039/d0md00162g |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM32644064X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM32644064X | ||
| 003 | DE-627 | ||
| 005 | 20240402233554.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1039/d0md00162g |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1360.xml |
| 035 | |a (DE-627)NLM32644064X | ||
| 035 | |a (NLM)34095841 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Manasa, Kesari Lakshmi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Design and synthesis of substituted (1-(benzyl)-1H-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone conjugates |b study on their apoptosis inducing ability and tubulin polymerization inhibition |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 02.04.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a This journal is © The Royal Society of Chemistry. | ||
| 520 | |a A library of substituted (1-(benzyl)-1H-1,2,3-triazol-4-yl)(piperazin-1-yl)methanone derivatives were designed, synthesized and screened for their in vitro cytotoxic activity against BT-474, HeLa, MCF-7, NCI-H460 and HaCaT cells by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among all the synthesized analogues, compound 10ec displayed the highest cytotoxicity with the IC50 value of 0.99 ± 0.01 μM towards BT-474 cancer cell line. The target compound (10ec) was also evaluated for its tubulin polymerization inhibition study. Detailed biological studies such as acridine orange/ethidium bromide (AO/EB), DAPI and annexin V-FITC/propidium iodide staining assay suggested that compound 10ec induced the apoptosis of BT-474 cells. The clonogenic assay revealed that the inhibition of colony formation in BT-474 cells by 10ec in concentration-dependent manner. Moreover, the flow cytometric analysis revealed that 10ec induced apoptosis via cell cycle arrest at the sub-G1 and G2/M phase. In silico studies of sulfonyl piperazine-integrated triazole conjugates unveil that they possess drug-like properties. According to the molecular modelling studies, compound 10ec binds to the colchicine binding site of the tubulin | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Thatikonda, Sowjanya |e verfasserin |4 aut | |
| 700 | 1 | |a Sigalapalli, Dilep Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Vuppaladadium, Sowmya |e verfasserin |4 aut | |
| 700 | 1 | |a Devi, Ganthala Parimala |e verfasserin |4 aut | |
| 700 | 1 | |a Godugu, Chandraiah |e verfasserin |4 aut | |
| 700 | 1 | |a Alvala, Mallika |e verfasserin |4 aut | |
| 700 | 1 | |a Nagesh, Narayana |e verfasserin |4 aut | |
| 700 | 1 | |a Babu, Bathini Nagendra |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t RSC medicinal chemistry |d 2020 |g 11(2020), 11 vom: 18. Nov., Seite 1295-1302 |w (DE-627)NLM320418669 |x 2632-8682 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2020 |g number:11 |g day:18 |g month:11 |g pages:1295-1302 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1039/d0md00162g |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2020 |e 11 |b 18 |c 11 |h 1295-1302 | ||