Novel dermacozine-1-carboxamides as promising anticancer agents with tubulin polymerization inhibitory activity

Abstract

In the present study, novel dermacozine-1-carboxamides (8a–8n) were synthesized and screened for their in vitro cytotoxic activity against three different cancer cell lines: MCF-7 (breast cancer), A-549 (lung cancer) and DU145 (prostate cancer).

Dermacozine N, the First Natural Linear Pentacyclic Oxazinophenazine with UV–Vis Absorption Maxima in the Near Infrared Region, along with Dermacozines O and P Isolated from the Mariana Trench Sediment Strain Dermacoccus abyssi MT 1.1T

“…In our recently published article on the full genome sequence of Dermacoccus abyssi MT 1.1 T and the isolation of dermacozine M (14), the strain was cultivated in a GYE seed culture medium initially, then subsequently large-scaled in 35 g/L ocean salt containing ISP2 medium [8]. Altering the preculture conditions has been shown to change the productivity of the strain when dermacozines H-J (11)(12)(13) were isolated [7]. Herein, we report on the isolation of further three dermacozines (1-3) produced by the strain Dermacoccus abyssi MT 1.1 T when a seed culture is grown in ISP2 medium containing 20 g/L NaCl, followed by a 35 g/L ocean salt supplemented ISP2 large-scale culture to approximate the deep-sea salinity of 34.7‰ [14].…”

“…Seven novel phenazines, dermacozines A-G (4-10), as novel phenazines originating from Dermacoccus abyssi strains MT 1.1 T and MT 1.2 were reported by our group in 2010. Subsequently, another four new derivatives: dermacozines H-J (11)(12)(13) and dermacozine M (14) were isolated and reported with the contribution of our group in 2014 and 2020, respectively (Figure 2) [6][7][8]. These highly pigmented dibenzo annulated pyrazines has kept our interest piqued toward finding further unknown derivatives.…”

“…Recently, a synthetic study revealed that the modulation of dermacozine-1-carboxamides, especially with electron releasing substituents (e.g., chloro-and methoxy groups) increases the in vitro anti-tubulin activity of dermacozine-1-carboxamide derivatives comparable to or even superior to the nocodazole control. This evidence gave us reason to further investigate this strain for additional bioactive dermacozine derivatives [11].…”

The Phenazine Scaffold Used as Cytotoxic Pharmacophore Applied in Bactericidal, Antiparasitic and Antitumor Agents

“…[110] Recently, Raman and coworkers [111] synthesized dermacozines A, B, and C, as well as a new series of dermacozine-1carboxamides. [112] The 3-pyridyl amide derivative; i. e., 6-chloro-5-methyl-N-(pyridin-3-yl)-5,10-dihydrophenazine-1-carboxamide ( 22) exhibited higher anticancer activity than other analogs with electron-donating groups, such as methoxy (À OMe) and À Cl moieties. This promising drug candidate was especially effective against the DU-prostate cancer cell line demonstrating the CTC 50 value of 6.32 μM.…”

“…Besides, benzo[ a ]phenazine derivatives showed activity against MT‐resistant strains [110] . Recently, Raman and coworkers [111] synthesized dermacozines A, B, and C, as well as a new series of dermacozine‐1‐carboxamides [112] . The 3‐pyridyl amide derivative; i. e ., 6‐chloro‐5‐methyl‐ N ‐(pyridin‐3‐yl)‐5,10‐dihydrophenazine‐1‐carboxamide ( 22 ) exhibited higher anticancer activity than other analogs with electron‐donating groups, such as methoxy (−OMe) and −Cl moieties.…”