Facile Synthesis and Cytotoxicity of Phenazine-Chromene Hybrid Molecules Derived from Phenazine Natural Product.
Comb Chem High Throughput Screen
; 22(1): 35-40, 2019.
Article
in En
| MEDLINE
| ID: mdl-30848195
ABSTRACT
AIM AND OBJECTIVE:
Small molecule targeted drugs can effectively reduce the toxicity and side effects of drugs, and improve the efficacy of drugs by their specific antitumor activity. Hence, the development of small molecular targeted drugs for cancer has important significance. This study was undertaken to design and synthesize novel phenazine-chromene hybrid molecules in order to optimize the structure and improve the efficacy of this kind of hybrids. MATERIALS ANDMETHODS:
O-diaminobenzene was used as starting material to synthesize twentyfour heterocyclic compounds designed as hybrid molecules of phenazine and 4H-chromene pharmacophores by facile methods. The structures of the compound were confirmed by 1H NMR, 13C NMR and HRMS. Furthermore, the synthesized compounds were evaluated for in vitro activity against four human cancer cell lines and two non-cancer cell lines by MTT test.RESULTS:
Some compounds showed strong cytotoxic activities against HepG2 and A549 cancer lines (IC50 = 5-10 µM). Comparing 2i with 2l, the introduction of hydrophilic groups on the phenazine core could not improve the antiproliferative activity significantly. Except 2d and 3c, compounds owning chlorine substituent on the 4H-chromene pharmacophore seemingly contribute to enhance the compounds' antiproliferative activity. Specially, compound 3c showed highest cytotoxicity against A549 cells with IC50 values of 3.3±0.4 µM. Furthermore, all compounds showed low or no cytotoxicity against HUVEC and L02 non-cancer cells in vitro.CONCLUSION:
Compound 3c may be used as potential lead molecule against A549 cancer cells.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenazines
/
Benzopyrans
/
Biological Products
/
Antineoplastic Agents, Phytogenic
Limits:
Humans
Language:
En
Journal:
Comb Chem High Throughput Screen
Journal subject:
BIOLOGIA MOLECULAR
/
QUIMICA
Year:
2019
Document type:
Article
Affiliation country:
China