STRUCTURE MODIFICATION OF ANDROGRAPHOLIDE TO IMPROVE ITS POTENCY AS ANTICANCER

https://doi.org/10.22146/ijc.21699

Hadi Poerwono(1*), Yoshiyuki Hattori(2), Hajime Kubo(3), Kimio Higashiyama(4)

(1) Faculty of Pharmacy, Airlangga University, Jl. Dharmawangsa Dalam, Surabaya 60286, Indonesia
(2) Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 152-8501, Japan
(3) Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 152-8501, Japan
(4) Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 152-8501, Japan
(*) Corresponding Author

Abstract


Andrographolide, a diterpenoid lactone isolated from the herb of Andrographis paniculata and known to possess antitumor activity in breast cancer models was subjected to semisynthesis leading to the preparation of a number of derivatives. After protection of the two hydroxyl groups present at C-3 and C-19 to give 3,19-isopropylidene and 3,19-benzylidene andrographolides, the remaining hydroxyl group at C-14 of andrographolide was treated with acid anhydride or acid chloride under base condition. Unfortunately, the reactions gave only 14-dehydroandrographolide as well as unidentified diacyl compounds in replace of the target molecule 14-O-acyl andrographolide. An alternative procedure using neat acetic anhydride under reflux gave the acetyl derivatives. The resulted compounds exhibited cytotoxic activity against MCF-7 breast cancer cells with better growth inhibition than the parent compound andrographolide.


Keywords


andrographolide; acylation; anticancer; cytotoxic; breast cancer cells

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References

[1] World Health Organization, 2002, WHO Monographs on Selected Medicinal Plants, Volume 2, WHO Graphics, Malta, pp 12-24.

[2] Shen, Y.C., Chen, C.F., and Chiou, W.F., 2002, J. Pharmacol., 35, 399-406.

[3] Calabrese, C., Berman, S.H., Babish, J.G., Ma, X., Shinto, L., Dorr, M., Wells, K., Wenner, C.A., and Standish, L.J., 2000, Phytother. Res., 14, 333-338.

[4] Puri, A., Saxena, R., Saxena, R.P., Saxena, K.C., Srivastava, V., and Tandon, J.S., 1993, J. Nat. Prod., 56, 995-999.

[5] See, D., Mason, S., and Roshan, R., 2002, Immunol. Invest., 31, 137-153.

[6] Zhang, X.F. and Tan, B.K., 2000, Clin. Exp. Pharmacol. Physiol., 27, 358-363.

[7] Zhang, C.Y. and Tan, B.K., 1996, Clin. Exp. Pharmacol. Physiol., 23, 675-678.

[8] Ajava, K.R., Sridevi, K., Vijaya, K.N., Nanduri, S., and Rajagopal, S., 2004, J. Ethnopharmacol., 92, 291-295.

[9] Misra, P., Pal, N.L., Guru, P.Y., Katiyar, J.C., Srivastava, V., and Tandon, J.S., 1992, Int. J. Pharmacog., 30, 263-274.

[10]Handa, S.S. and Sharma, A., 1990, Indian J. Med. Res., 92, 276-283.

[11]Siripong, P., Kongkathip, B., Preechanukool, K., Picha, P., Tunsuwan, K., and Taylor, W.C., 1992, J. Sci. Soc. Thailand, 18, 187-194.

[12]Fujita, T., Fujitani, Y., Takeda, Y., Takaishi, Y., Yamada, T., Kido, M., and Miura, I., 1984, Chem. Pharm. Bull., 32, 2117-2122.

[13]Matsuda, T., Kuroyanagi, M., Sugiyama, S., Umehara, K., Ueno, A., and Nishi, K., 1994, Chem. Pharm. Bull., 42, 1216-1225.

[14]Sharma, A., Krishan, L., and Handa, S.S., 1992, Phytochem. Anal., 3, 129-131.

[15]Rajani, M., Shrivastava, N., and Ravishankara, M.M., 2000, Pharm. Biol., 38, 204-209.

[16]Rajagopal, S., Ajava, K.R., Deevi, D.S., Satyanayarana, C., and Rajagopalan, R., 2003, J. Expt. Ther. Oncol., 3, 147-158.

[17]Nanduri, S., Pothukuchi, S., Rajagopal, S., Venkateswarlu, A., Pillai, S.B.K., and Chakrabarti, R., 2002, Novel anticancer compounds: process for their preparation and pharmaceutical compositions containing them, US Patent, Application No. 20020016363.

[18]Nanduri, S., Rajagopal, S., Pothukuchi, S., Pillai, S.B.K., and Chakrabarti, R., 2002, Novel compounds having antitumor activity: process for their preparation and pharmaceutical compositions containing them, US Patent, Application No. 20020032229.

[19]Nanduri, S., Nyavanandi, V. K., Thunuguntla, S.S.R., Kasu, S., Pothukuchi, S.R., Rajagopal, S., Deevi, D.S., Reka, A.K., Ramanujam, R., and Akella, V., 2003, Synthesis and Evaluation of Novel Ester Analogs of Andrographolide as Potent Anticancer Agents, Poster Session Code No. MEDI 93, The 225th ACS National Meeting, New Orleans, LA.

[20]Nanduri, S., Nyavanandi, V. K., Thunuguntla, S.S.R., Kasu, S., Pallerla, M.K., Ram, P.S., Rajagopal, S., Kumar, R.A., Rajagopalan, R., Babu, J.M., Vyas, K., Devi, A.S., Reddy, G.O., and Akella, V., 2004, Bioorg. Med. Chem. Lett., 14, 4711-4717.

[21]Jada, S.R., Hamzah, A.S., Lajis, N.H., Saad, M.S., Stevens, M.F.G., and Stanslas, J., 2006, J. Enzyme Inhib. Med. Chem., 21, 145-155.

[22]He, X., Li, J., Gao, H., Qiu, F., Hu, K., Cui, X., and Yao, X., 2003, Drug Metab. Dispos., 31, 983-985.



DOI: https://doi.org/10.22146/ijc.21699

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