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Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line.

Molatlhegi RP, Phulukdaree A, Anand K, Gengan RM, Tiloke C, Chuturgoon AA - PLoS ONE (2015)

Bottom Line: Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity.ECAP was synthesized as a yellow powder with melting point of 240-247 °C.ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production.

View Article: PubMed Central - PubMed

Affiliation: Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, RSA.

ABSTRACT
Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer.

No MeSH data available.


Related in: MedlinePlus

Characterization of the novel (Z)-4-((9-ethyl-9H-carbazol-3-yl) amino) pent-3-en-2-one (ECAP).(A) IR, (B) 1H-NMR and (C) 13C-NMR spectrums.
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pone.0129874.g002: Characterization of the novel (Z)-4-((9-ethyl-9H-carbazol-3-yl) amino) pent-3-en-2-one (ECAP).(A) IR, (B) 1H-NMR and (C) 13C-NMR spectrums.

Mentions: The resulting product was a yellow solid produced in 94% yield; melting point (mp): 240–247°C. Functional groups were predicted using IR (KBr, cm-1): 1774.97 (C = O), 3043.92 (N-H), 2988.76 (C-H) Alkanes, 1562.66 (C = C) Aromatic rings (Fig 2A). The 1H-NMR (400 MHz, CDCl3) was used to predict the ratio of the hydrogen number: δ (ppm) 12.59 (s, 1H), 8.20 (q, 1H), 7.8 (d, 1H), 7.45–7.40 (m, 2H), 7.35–7.30 (m, 3H), 5.3 (s, 1H), 4.35 (q, 2H), 2.25 (s, 3H) 1.95 (s, 3H), 1.45 (t, 3H) (Fig 2B). The 13C-NMR (400 MHz, CDCl3) was further used to predict the backbone of the molecule: δ (ppm) 195.67, 191.20, 161.94, 140.51, 138.18, 130.13, 126.39, 126.18, 123.93, 123.15, 122.47, 121.00, 120.52, 119.00, 117.65, 109.32, 108.72, 108.59, 96.60, 37.70, 29.08, 27.84, 19.80, 13.82, 13.72 (Fig 2C).


Cytotoxic Effect of a Novel Synthesized Carbazole Compound on A549 Lung Cancer Cell Line.

Molatlhegi RP, Phulukdaree A, Anand K, Gengan RM, Tiloke C, Chuturgoon AA - PLoS ONE (2015)

Characterization of the novel (Z)-4-((9-ethyl-9H-carbazol-3-yl) amino) pent-3-en-2-one (ECAP).(A) IR, (B) 1H-NMR and (C) 13C-NMR spectrums.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4489925&req=5

pone.0129874.g002: Characterization of the novel (Z)-4-((9-ethyl-9H-carbazol-3-yl) amino) pent-3-en-2-one (ECAP).(A) IR, (B) 1H-NMR and (C) 13C-NMR spectrums.
Mentions: The resulting product was a yellow solid produced in 94% yield; melting point (mp): 240–247°C. Functional groups were predicted using IR (KBr, cm-1): 1774.97 (C = O), 3043.92 (N-H), 2988.76 (C-H) Alkanes, 1562.66 (C = C) Aromatic rings (Fig 2A). The 1H-NMR (400 MHz, CDCl3) was used to predict the ratio of the hydrogen number: δ (ppm) 12.59 (s, 1H), 8.20 (q, 1H), 7.8 (d, 1H), 7.45–7.40 (m, 2H), 7.35–7.30 (m, 3H), 5.3 (s, 1H), 4.35 (q, 2H), 2.25 (s, 3H) 1.95 (s, 3H), 1.45 (t, 3H) (Fig 2B). The 13C-NMR (400 MHz, CDCl3) was further used to predict the backbone of the molecule: δ (ppm) 195.67, 191.20, 161.94, 140.51, 138.18, 130.13, 126.39, 126.18, 123.93, 123.15, 122.47, 121.00, 120.52, 119.00, 117.65, 109.32, 108.72, 108.59, 96.60, 37.70, 29.08, 27.84, 19.80, 13.82, 13.72 (Fig 2C).

Bottom Line: Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity.ECAP was synthesized as a yellow powder with melting point of 240-247 °C.ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production.

View Article: PubMed Central - PubMed

Affiliation: Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, RSA.

ABSTRACT
Increased death rates due to lung cancer have necessitated the search for potential novel anticancer compounds such as carbazole derivatives. Carbazoles are aromatic heterocyclic compounds with anticancer, antibacterial and anti-inflammatory activity. The study investigated the ability of the novel carbazole compound (Z)-4-[9-ethyl-9aH-carbazol-3-yl) amino] pent-3-en-2-one (ECAP) to induce cytotoxicity of lung cancer cells and its mechanism of action. ECAP was synthesized as a yellow powder with melting point of 240-247 °C. The 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), lipid peroxidation and comet assays were used to assess the cytotoxic effect of the compound on A549 lung cancer cells. Protein expression was determined using western blots, apoptosis was measured by luminometry (caspase-3/7, -8 and -9) assay and flow cytometry was used to measure phosphatidylserine (PS) externalisation. ECAP induced a p53 mediated apoptosis of lung cancer cells due to a significant reduction in the expression of antioxidant defence proteins (Nrf2 and SOD), Hsp70 (p < 0.02) and Bcl-2 (p < 0.0006), thereby up-regulating reactive oxygen species (ROS) production. This resulted in DNA damage (p < 0.0001), up-regulation of Bax expression and caspase activity and induction of apoptosis in lung cancer cells. The results show the anticancer potential of ECAP on lung cancer.

No MeSH data available.


Related in: MedlinePlus