Synthesis and biological evaluation of purine-pyrazole hybrids incorporating thiazole, thiazolidinone or rhodanine moiety as 15-LOX inhibitors endowed with anticancer and antioxidant potential
Copyright © 2019 Elsevier Inc. All rights reserved..
Novel purine-pyrazole hybrids combining thiazoles, thiazolidinones and rhodanines, were designed and tested as 15-LOX inhibitors, potential anticancer and antioxidant agents. All tested compounds were found to be potent 15-LOX inhibitors with IC50 ranging from 1.76 to 6.12 µM. The prepared compounds were evaluated in vitro against five cancer cell lines: A549 (lung), Caco-2 (colon), PC3 (prostate), MCF-7 (breast) and HepG-2 (liver). Compounds 7b and 8b displayed broad spectrum anticancer activity against the five tested cell lines (IC50 = 18.5-95.39 µM). While, compound 7h demonstrated moderate anticancer activity against lung A549 and colon Caco-2 cell lines. Antioxidant screening revealed that six compounds (5a, 5b, 6b, 7b, 7h and 8b) with IC50 ranging from 0.93 to 14.43 µg/ml were found to be more potent scavengers of 2,2- diphenyl-1-picrylhydrazyl (DPPH) than the reference ascorbic acid with IC50 value of 15.34 µg/ml. Compounds 7b, 7h and 8b, when evaluated for their antioxidant activity, where found to be potent DPPH scavengers. Moreover, compound 7b displayed twice the potency of ascorbic acid as NO scavenger. Docking study was performed to elucidate the possible binding mode of the most active compounds with the active site of 15-LOX enzyme. Collectively, the purine-pyrazole hybrids having thiazoline or thizolidinone moieties (7b, 7h and 8b) constitute a promising scaffold in designing more potent 15-LOX inhibitors with anticancer and antioxidant potential.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:87 |
|---|---|
| Enthalten in: |
Bioorganic chemistry - 87(2019) vom: 01. Juni, Seite 821-837 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Afifi, Ola S [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 22.09.2020 Date Revised 22.09.2020 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.bioorg.2019.03.076 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM296196215 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM296196215 | ||
| 003 | DE-627 | ||
| 005 | 20231225085320.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.bioorg.2019.03.076 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0987.xml |
| 035 | |a (DE-627)NLM296196215 | ||
| 035 | |a (NLM)30999135 | ||
| 035 | |a (PII)S0045-2068(19)30015-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Afifi, Ola S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Synthesis and biological evaluation of purine-pyrazole hybrids incorporating thiazole, thiazolidinone or rhodanine moiety as 15-LOX inhibitors endowed with anticancer and antioxidant potential |
| 264 | 1 | |c 2019 | |
| 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 Completed 22.09.2020 | ||
| 500 | |a Date Revised 22.09.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2019 Elsevier Inc. All rights reserved. | ||
| 520 | |a Novel purine-pyrazole hybrids combining thiazoles, thiazolidinones and rhodanines, were designed and tested as 15-LOX inhibitors, potential anticancer and antioxidant agents. All tested compounds were found to be potent 15-LOX inhibitors with IC50 ranging from 1.76 to 6.12 µM. The prepared compounds were evaluated in vitro against five cancer cell lines: A549 (lung), Caco-2 (colon), PC3 (prostate), MCF-7 (breast) and HepG-2 (liver). Compounds 7b and 8b displayed broad spectrum anticancer activity against the five tested cell lines (IC50 = 18.5-95.39 µM). While, compound 7h demonstrated moderate anticancer activity against lung A549 and colon Caco-2 cell lines. Antioxidant screening revealed that six compounds (5a, 5b, 6b, 7b, 7h and 8b) with IC50 ranging from 0.93 to 14.43 µg/ml were found to be more potent scavengers of 2,2- diphenyl-1-picrylhydrazyl (DPPH) than the reference ascorbic acid with IC50 value of 15.34 µg/ml. Compounds 7b, 7h and 8b, when evaluated for their antioxidant activity, where found to be potent DPPH scavengers. Moreover, compound 7b displayed twice the potency of ascorbic acid as NO scavenger. Docking study was performed to elucidate the possible binding mode of the most active compounds with the active site of 15-LOX enzyme. Collectively, the purine-pyrazole hybrids having thiazoline or thizolidinone moieties (7b, 7h and 8b) constitute a promising scaffold in designing more potent 15-LOX inhibitors with anticancer and antioxidant potential | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a Antioxidants |2 NLM | |
| 650 | 7 | |a Biphenyl Compounds |2 NLM | |
| 650 | 7 | |a Lipoxygenase Inhibitors |2 NLM | |
| 650 | 7 | |a Picrates |2 NLM | |
| 650 | 7 | |a Purines |2 NLM | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Thiazoles |2 NLM | |
| 650 | 7 | |a Thiazolidines |2 NLM | |
| 650 | 7 | |a pyrazole |2 NLM | |
| 650 | 7 | |a 3QD5KJZ7ZJ |2 NLM | |
| 650 | 7 | |a Rhodanine |2 NLM | |
| 650 | 7 | |a 7O50LKL2G8 |2 NLM | |
| 650 | 7 | |a 1,1-diphenyl-2-picrylhydrazyl |2 NLM | |
| 650 | 7 | |a DFD3H4VGDH |2 NLM | |
| 650 | 7 | |a Arachidonate 15-Lipoxygenase |2 NLM | |
| 650 | 7 | |a EC 1.13.11.33 |2 NLM | |
| 650 | 7 | |a purine |2 NLM | |
| 650 | 7 | |a W60KTZ3IZY |2 NLM | |
| 700 | 1 | |a Shaaban, Omaima G |e verfasserin |4 aut | |
| 700 | 1 | |a Abd El Razik, Heba A |e verfasserin |4 aut | |
| 700 | 1 | |a Shams El-Dine, Shams El-Dine A |e verfasserin |4 aut | |
| 700 | 1 | |a Ashour, Fawzia A |e verfasserin |4 aut | |
| 700 | 1 | |a El-Tombary, Alaa A |e verfasserin |4 aut | |
| 700 | 1 | |a Abu-Serie, Marwa M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Bioorganic chemistry |d 1986 |g 87(2019) vom: 01. Juni, Seite 821-837 |w (DE-627)NLM012846570 |x 1090-2120 |7 nnns |
| 773 | 1 | 8 | |g volume:87 |g year:2019 |g day:01 |g month:06 |g pages:821-837 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bioorg.2019.03.076 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 87 |j 2019 |b 01 |c 06 |h 821-837 | ||