- Design, Synthesis and Structure-Activity Relationship Studies of Glycosylated Derivatives of Marine Natural Product Lamellarin D
-
Lamellarin D, a marine natural product, acts as a potent inhibitor of DNA topoisomerase I (Topo I). To modify its physicochemical property and biological activity, a series of mono- and di-glycosylated derivatives were designed and synthesized through 22–26 multi-steps. Their inhibition of human Topo I was evaluated, and most of the glycosylated derivatives exhibited high potency in inhibiting Topo I activity as well as lamellarin D. All the 15 target compounds were evaluated for their cytotoxic activities against five human cancer cell lines. The typical lamellarin derivative ZL?3 exhibited the best activity with IC50 values of 3 nM, 10 nM, and 15 nM against human lung cancer A549 cells, human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells. Compound ZL?1 exhibited anti-cancer activity with IC50 of 14 nM and 24 nM against human colon cancer HCT116 cells and human hepatocellular carcinoma HepG2 cells, respectively. Cell cycle analysis in MDA-MB-231 suggested ZL?3 inhibited cell growth through arresting cells at the G2/M phase of the cell cycle. Further tests showed a significant improvement in aqueous solubility of ZL?1 and ZL?7. This study suggested that glycosylation could be utilized as a useful strategy to optimize lamellarin D derivatives as Topo I inhibitors and anticancer agents.
- Zheng, Liuliu,Gao, Tingting,Ge, Zhiwei,Ma, Zhongjun,Xu, Jinzhong,Ding, Wanjing,Shen, Li
-
-
- Synthesis and biological evaluation of novel chromonyl enaminones as α-glucosidase inhibitors
-
Series of novel chromonyl enaminones 1a–e and 2a–e and 3-alkylated chromones 3a–e were synthesized and evaluated in vitro as α-glucosidase inhibitors as well as antioxidant and antifungal agents. Antifungal activity was tested on strains of Candida albicans. Compounds 2a and 2d–e showed good inhibition of the α-glucosidase enzyme (IC50 = 5.5, 0.9, and 1.5 mM, respectively), their effect being better than that of 1a–e, 3a–e, and acarbose (the standard, IC50 = 7.73 ± 0.9 mM). The structure–activity relationship suggests that the phenyl group at the C-3 position of the chromone ring system and the 4-chlorophenyl group at the enaminone moiety (derivatives 2) increased the inhibition of α-glucosidase. Compounds 2a–e exhibited a slight antioxidant effect, and compounds 3a–e a moderate antifungal activity against C. albicans (IC50 70.5–83.1 μg/mL). Docking studies revealed that compounds 2 interact with the α-glucosidase residues of the binding pocket. Therefore, these chromone derivatives may be considered as potential α-glucosidase inhibitors, as well as antifungal agents against some Candida strains of yeast.
- Mendieta-Moctezuma, Aarón,Rugerio-Escalona, Catalina,Villa-Ruano, Nemesio,Gutierrez, Rsuini U.,Jiménez-Montejo, Fabiola E.,Fragoso-Vázquez, M. Jonathan,Correa-Basurto, José,Cruz-López, María C.,Delgado, Francisco,Tamariz, Joaquín
-
p. 831 - 848
(2019/04/25)
-
- LYSYL OXIDASE-LIKE 2 INHIBITORS AND USES THEREOF
-
Described herein are compounds that are LOXL2 inhibitors, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with LOXL2 activity.
- -
-
Paragraph 00419; 00420
(2017/02/24)
-
- Design and total synthesis of Mannich derivatives of marine natural product lamellarin D as cytotoxic agents
-
Enlightened by the modification route from Camptothecin (CPT) to Topotecan and based on classical drug design theory, a series of Mannich derivatives of lamellarin D were designed and synthesized in 26-27 steps starting from vanillin and isovanilin. All synthesized compounds were then biologically evaluated for their in vitro anti-cancer activities and Topo I inhibitory activities. The results showed that most target compounds exhibited Topo I inhibitory activities in equivalent level with that of lamellarin D. Compound SL-9 exhibited better Topo I inhibitory activity than that of lamellarin D. Compounds SL-2, SL-3, SL-4, SL-5 and SL-11 exhibited better anti-proliferative activity against HT-29 cells than that of lamellarin D.
- Shen, Li,Xie, Nan,Yang, Bo,Hu, Yongzhou,Zhang, Yongmin
-
p. 807 - 817
(2014/10/15)
-
- Practical synthesis of glaziovianin A, a cytotoxic isoflavone, and its O7-propargyl analogue
-
Glaziovianin A and its O7-propargyl analogue are potent cytotoxic isoflavones. We found that the O7-propargyl analogue completely arrested cell-cycle progression. We have achieved the large-scale synthesis of glaziovianin A and its O7-propargyl analogue for further in vivo experimentation.
- Hayakawa, Ichiro,Shioda, Shuya,Ikedo, Akiyuki,Kigoshi, Hideo
-
p. 544 - 549
(2014/05/06)
-
- SYNTHESIS OF 13C-LABELLED ESTROGEN ANALOGUES
-
There is provided a method of producing novel 13C-labelled estrogen analogues. The method preferably proceeds via an intermediate A or B or which is a mixture of (A) or (B): wherein a13C atom is located at one or more of positions 1, 2, 3 or 4 and wherein R is an optionally substituted alkane, alkene, alkyne or aryl group. Preferably R is -CH2Ph. An alternative preferred intermediate compound is 13C-resorcinol.
- -
-
-
- The synthesis of [2,3,4-13C3]glycitein
-
Glycitein is one of the soy isoflavones which have attracted considerable interest in recent years due to their possible beneficial effects on human health. However, glycitein has been much less studied than other members of this family due to the lack of
- Zhang, Qingzhi,Botting, Nigel P.
-
p. 12211 - 12216
(2007/10/03)
-