Pirenoxine Synthesis Essay
Belanger, J., Balakrishna, M., Latha, P., Katumalla, S., Johns, T., 2010. Contribution of selected wild and cultivated leafy vegetables from South India to lutein and beta-carotene intake. Asia Pac. J. Clin. Nutr. 19, 417-424. [ Links ]
Bhakuni, D.S., Dhar, M.L., Dhar, M.M., Dhawan, B.N., Mehrotra, B.N., 1969. Screening of Indian plants for biological activity. Part II. Indian J. Exp. Biol. 7, 250-262. [ Links ]
Bhatia, H., Sharma, Y.P., Manhas, R.K., Kumar, K., 2014. Ethnomedicinal plants used by the villagers of district Udhampur, J&K, India. J. Ethnopharmacol. 151, 1005-1018. [ Links ]
Bhujbal, S.S., Chitlange, S.S., Suralkar, A.A., Shinde, D.B., Patil, M.J., 2008. Anti-inflammatory activity of an isolated flavonoid fraction from Celosia argentea Linn. J. Med. Plants Res. 2, 52-54. [ Links ]
Board, F.o.C.e., 2003. Flora of China. http://foc.eflora.cn/ . [ Links ]
Cai, Y.Z., Sun, M., Corke, H., 2005. HPLC characterization of betalains from plants in the Amaranthaceae. J. Chromatogr. Sci. 43, 454-460. [ Links ]
Chen, R.B., Zhang, Y.Y., He, J.M., Wu, W.D., Guo, M.L., 2015. Simultaneous Determination of Two Major Triterpenoid Saponins Celosin I and Celosin II in Celosiae Semen by HPLC-ELSD. Chinese J. CHM 7, 185-190. [ Links ]
Chen, Z.Y., Li, W.L., Zhao, H., Song, X.F., Guo, X.L., Wei, H.J., 2005. Effect of Celosia cristata L. flavonoid on expression of bone morphogenetic protein and function of tubular reabsorption of rats with diabete mellitus. Chinese J. Clin. Rehabil 39, 188-190. [ Links ]
Cheng, Q.L., Li, H.L., Huang, Z.Q., 2013. Study on apoptosis of HepG2 cell induced by celosin A from Celosia Semen and its mechanism. Chinese J. Exp. Tradit. Med. Form. 19, 200-204. [ Links ]
Chi, X., Guo, M.L., Song, H., Chen, Y.D., 2010. Study on chemical constituents of Celosia cristata seed. J. Jilin Agric. Univ. 32, 657-660. [ Links ]
Devhare, S.V., Nirmal, S.A., Rub, R.A., Dhasade, V.V., Zaware, B.B., Mandal, S.C., 2011. Immunomodulating activity of Celosia argentea Linn aerial parts. Lat. Am. J. Pharm. 30, 168-171. [ Links ]
Faboya, O.O.P., 1990. The effect of pre-process handling conditions on the ascorbic acid content of green leafy vegetables. Food Chem. 38, 297-303. [ Links ]
Feng, N., Xue, Q., Guo, Q.H., Zhao, R., Guo, M.L., 2009. Genetic diversity and population structure of Celosia argentea and related species revealed by SRAP. Biochem. Genet. 47, 521-532. [ Links ]
Fu, H.Z., Meng, X.Y., Li, S.S., Wu, L.J., 1992. Study on the chemical constituents of Semen Celosiae. Chinese Tradit. Herbal Drugs 23, 344-345. [ Links ]
Gnanamani, A., Priya, K.S., Radhakrishnan, N., Babu, M., 2003. Antibacterial activity of two plant extracts on eight burn pathogens. J. Ethnopharmacol. 86, 59-61. [ Links ]
Guo, Q.H., Guo, M.L., Xue, Q., Feng, N., Zhang, H.M., 2008. Establishment and optimization of sequence-related amplified polymorphism system for Celosia argentea. Chinese Trad. Herbal Drug 39, 264-266. [ Links ]
Hase, K., Basnet, P., Kadota, S., Namba, T., 1997. Immunostimulating activity of celosian, an antihepatotoxic polysaccharide isolated from Celosia argentea. Planta Med. 63, 216-219. [ Links ]
Hase, K., Kadota, S., Basnet, P., Takahashi, T., Namba, T., 1996. Protective effect of celosian, an acidic polysaccharide, on chemically and immunologically induced liver injuries. Biol. Pharm. Bull. 19, 567-572. [ Links ]
Hayakawa, Y., Fujii, H., Hase, K., Ohnishi, Y., Sakukawa, R., Kadota, S., Namba, T., Saiki, I., 1998. Anti-metastatic and immunomodulating properties of the water extract from Celosia argentea seeds. Biol. Pharm. Bull. 21, 1154-1159. [ Links ]
Hayato, S., Hiroshi, M., Shigeo, I., Jun'chi, K., 2003. New antimitotic bicyclic peptides, celogentins D–H, and J, from the seeds of Celosia argentea. Tetrahedron 59, 5307-5315. [ Links ]
Hayato, S., Hiroshi, M., Motoo, S., Jun'ichi, K., 2004. Celogentin K, a new cyclic peptide from the seeds of Celosia argentea and X-ray structure of moroidin. Tetrahedron. 60, 2489-2495. [ Links ]
Huang, G.X., 1987. Ben cao qiu zhen. People's Medical Publish House Beijing, pp. 167. [ Links ]
Huang, X.R., Qi, M.X., Wang, Z.Y., Wang, Y., 2004. Effects of four Chinese herbs which pass through liver-channel on expression of Bcl-2 and Bax in rat lens epithelial cells. Chinese J. Clin. Pharmacol. Ther. 9, 322-325. [ Links ]
Huang, X.R., Qi, M.X., Wang, Z.Y., Wang, Y., 2004. Effects of four Chinese herbs which pass through liver-channel on improving eyesight and protecting oxidative injury of lens and apoptosis of lens epithelial cells. Chinese J. Clin. Pharmacol. Ther. 9, 441-446. [ Links ]
Huang, Z.Q., Cheng, Q.L., Li, H.L., Huang, C., 2013. The study for apoptosis of human cervical cancer HeLa cell induced by celosin A from Celosiae Semen and its mechanisms. Acta Pharmacol. Sin. 34, 7. [ Links ]
Huang, Z.Q., Jiao, L.Y., 2013. Determination of seven metal elements in Gannan Semen Celosiae by atomic absorption spectrometry. Guangdong Wei Liang Yuan Su Ke Xue 20, 6-9. [ Links ]
Jiang, X.M., Guo, H., Sun, W.Q., Tong, D.Q., Chen, Y., 2003. Research of Celosia cristata on increasing immunity and suppressor tumor of S180 ascites cancer mice. J. Beihua Univ. (Natural Science) 4, 123-124. [ Links ]
Kim, Y.S., Hwang, J.W., Sung, S.H., Jeon, Y.J., Jeong, J.H., Jeon, B.T., Moon, S.H., Park, P.J., 2015. Antioxidant activity and protective effect of extract of Celosia cristata L. flower on tert-butyl hydroperoxide-induced oxidative hepatotoxicity. Food Chem. 168, 572-579. [ Links ]
Kiritikar, K.R., Basu, B.D., 1987. Indian Medicinal Plants, vol. I., 2nd ed. International Book Distributors, pp. 2052–2055. [ Links ]
Kobayashi, J., Suzuki, H., Shimbo, K., Takeya, K., Morita, H., 2001. Celogentins A–C, new antimitotic bicyclic peptides from the seeds of Celosia argentea. J. Org. Chem. 66, 6626-6633. [ Links ]
Li, S.Z., 2003. Ben cao gang mu. China Pictorial Publishing House, Beijing, pp. 77. [ Links ]
Li, W.L., Tian, Y.H., Shen, G.X., 2003. Effect of flavonoid of Celosia cristata on mineralization and ICF-1 expression. China J. Publ. Health 19, 1392-1393. [ Links ]
Li, W.L., Zhao, H., Chen, Z.Y., Wei, H.J., Guo, X.L., 2006. Preventive effect of Celosia cristata L. flavonoid on osteoporosis in ovariectomized rats. China J. Publ. Health 22, 165-166. [ Links ]
Lin, W.Q., Chen, Z., Liu, J.Q., 2002. The chemical constituents of Perilla frutescens (L.) Britt. var. acute (Thunb.) and Celosia argentea L. seeds grown in Fujian province. Chinese Acad. Med. Magazing Organisms , 57-59. [ Links ]
Liu, A., Cao, M.F., Xu, C.Y., Jin, W.E., Pan, X.D., Yu, H.Q., Guan, L.H., 2007. The clinical observation of treatment of 20% water extracts of Semen Celosiae on senile cataract. J. Fujian College TCM 17, 10-11. [ Links ]
Ma, X.G., 2012. Comparative study on Semen Celosiae, Semen critata and
Neoplastic cells need higher concentrations of iron and copper for their growth than normal cells [1,2], so the development of novel Fe and Cu chelators has become a promising anticancer strategy owing to their ability to inhibit cancer cell proliferation . Accordingly, triapine, an iron chelator, is currently in phase II clinical trials . Recently, a Dp44mT analog, di-2-pyridylketone-2-pyridine carboxylic acid hydrazone (DPPCAH) showed markedly antitumor activity against numerous cancer cell lines. This antitumor mechanism was mediated by its ability to inhibit topoisomerase, leading to cell cycle arrest and induction of DNA fragmentation . Its copper complex, (DPPCAH-Cu) exhibited similar but stronger antitumor activity as indicated by several studies [6,7]. Many anticancer drugs have potent metal chelating ability. These metal chelators, especially copper chelates, possess enhanced biological activity compared to the non-chelating drugs. Mechanistic studies have revealed that the difference is at least partially related to the redox features of the copper complexes [5,8,9]. However, information related to the effect of the interactions of metal chelating agents with biological molecules, such as human serum albumin (HSA) or bovine serum albumin (BSA) and DNA and their contribution to cytotoxicity has received limited attention. DNA and proteins (especially enzymes) are of particular interest as targets for a wide range of anticancer and antibiotic drugs . To understand the nature, structure and behavior of drugs in biological systems, studies related to drug interactions with proteins and DNA are required.
The biological activity of any drug is influenced by drug-protein interactions. Proteins, mainly HSA and bovine serum albumin (BSA) are extensively studied examples, as they are the most important carriers for a broad spectrum of exogenous and endogenous ligands. HSA-drug(s) interactions greatly influence the absorption, distribution, metabolism and excretion of drugs [11,12]. Recently, Merlot et al., reported the cellular uptake of Dp44mT as a novel mechanism facilitated by human serum albumin (HSA) . Accumulation of albumin occurs within the interstitium of solid tumors [14,15,16]. Chemically, BSA is a heart-shaped globular protein, containing three homologous domains (I, II, and III), and each domain includes, two sub-domains (IA and IB) . BSA contains two tryptophan (Trp) residues, one (Trp134) is located on the surface of subdomain IB, and Trp213 located within the hydrophobic binding pocket of subdomain IIA. The interaction of BSA with endogenous and exogenous ligands mostly occurs in these domains.
The objective of the present study was to find the specific binding domains of BSA and DPPCAH by employing computer-aided molecular docking and spectral techniques. Numerous methods are available for investigating protein-ligand binding, such as equilibrium dialysis, fluorescence, calorimetry, and nuclear magnetic resonance , yet spectral techniques are widely used in determining the ligand and biomacromolecule interactions, hence our choice. Special emphasis is placed on determining the binding affinity of the DPPCAH and DPPCAH-Cu towards BSA, which could provide additional insight into the differences in antitumor activity detected between these ligands (with metal chelating ability) and their metal complexes.
2. Results and Discussion
2.1. BSA Mediated Cytotoxicity of DPPCAH and Its Copper Complex (DPPCAH-Cu)
It has been reported that HSA could enhance the anti-proliferative activity of Dp44mT . Thus, we examined the effect of BSA on both DPPCAH- and DPPCAH-Cu-mediated inhibition of HepG2 cells in which BSA was the main protein source in the cell culture. As shown in Figure 1, BSA attenuated the growth inhibition of HepG2 cells mediated by DPPCAH, but not DPPCAH-Cu, indicating that the effect of BSA on uptake or cytotoxicity of the drug was drug dependent, which was consistent with earlier reports .
Previously, we demonstrated that DPPCAH significantly inhibited the growth inhibition of HepG2 cells (IC50: 4.6 ± 0.2 μM), while DPPCAH-Cu significantly enhanced the antitumor activity . In this regards, the weaker anti-proliferative activity of DPPCAH might have be due to the abatement of BSA. Hence, a study related to their interactions was necessary.
2.2. Interactions of DPPCAH and DPPCAH-Cu with BSA
The two Trp residues of BSA are normally used as intrinsic fluorophores in spectral studies. Fluorescence quenching analyses of these Trp residues provides information regarding the interaction of the drug as quencher with BSA, revealing the mechanism(s) whereby small molecules bind to proteins. Figure 2 shows the fluorescence quenching spectra of BSA with varying concentrations of the DPPCAH and DPPCAH-Cu. The fluorescence intensities of BSA gradually decreased with the addition of the above drugs, suggesting that both DPPCAH and DPPCAH-Cu could associate with BSA. Notably, a bathochromic red shift occurred upon addition of DPPCAH (Figure 2a), unlike the blue shift induced by DPPCAH-Cu (Figure 2b), indicating that the investigated agents had different effects on the environment of Trp residues. The red shift specifies Trp residues exposed to the solvent, whereas the blue shift is a consequence of Trp residues located in a more hydrophobic environment .
2.3. Binding Sites and Binding Constants
2.4. Binding Sites and Binding Constants
2.5. Binding Forces
Values of ΔH, ΔS, and ΔG for DPPCAH and DPPCAH-Cu binding to BSA are listed in Table 1. The negative value of ΔG reveals that the interaction process was spontaneous.