Synthesis, Spectroscopic, and in Vitro Cytotoxic Studies of Fatty Acid Analogues of 2, 6-Diisopropylphenol
Ali Mohammad, Fauzia B. Faruqi, Jamal Mustafa
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DOI: 10.4236/jct.2010.13020   PDF    HTML   XML   4,624 Downloads   9,293 Views   Citations

Abstract

This paper represents the synthesis, spectral analysis and in-vitro cytotoxic studies of some novel fatty acid anti-cancer conjugates of 2, 6-diisopropylphenol (propofol). Propofol is a potent intravenous hypnotic agent which is widely used for the induction and maintenance of anesthesia and for sedation in the intensive care unit. Propofol also possess anti-cancer properties in addition to its sedative effects. Cytotoxicity of all the synthesized compounds was examined against human HeLa cancer cell lines. The anti-cancer screening of these novel drug candidates suggest that all of them reported here may be useful for the treatment of cancer as all of them exhibited significant anticancer activity against human HeLa cancer cell lines. The results indicate that these novel drug candidates might represent a new class of anticancer agents.

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A. Mohammad, F. Faruqi and J. Mustafa, "Synthesis, Spectroscopic, and in Vitro Cytotoxic Studies of Fatty Acid Analogues of 2, 6-Diisopropylphenol," Journal of Cancer Therapy, Vol. 1 No. 3, 2010, pp. 124-130. doi: 10.4236/jct.2010.13020.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] H. Covington, “Use of Propofol for Sedation in the ICV,” Critical Care Nursing, Vol. 18, No. 5, 1998, pp. 34-39.
[2] R. D. Miller, “Local Anesthetics: Anesthesia,” In: R. D. Miller, Ed., Local Anesthetics, Churchill Livingstone, New York, Vol. 5, 2000, pp. 491-521.
[3] O. Eriksson, P. Pollesello and N. E. Seris, “Inhibition of Lipid Peroxidation in Isolated Rat Liver Mitochondria by the General Anesthetic Propofol,” Biochemical Pharmacology, Vol. 44, No. 2, 1992, pp. 391-393.
[4] P. G. Murphy, D. S. Myers, M. J. Davies, N. R. Webster and J. G. Jones, “The Antioxidant Potential of Propofol,” British Journal of Anesthesia, Vol. 68, No. 6, 1992, pp. 613-618.
[5] M. Tsuchiya, A. Asada, K. Maeda, Y. Ueda, E. F. Sato, M. Shindo and M. Inove, “Propofol versus Medazolam Regarding their Antioxidant Activities,” American Journal of Respiratory and Critical Care Medicine, Vol. 163, No. 1, 2001, pp. 26-31.
[6] H. C. Hemming and A. I. Adamo, “Effects of Halothane and Propofol on Purified Brain Protein Kinase C Activation,” Anesthesiology, Vol. 81, No. 1, 1994, pp. 147-155.
[7] N. Kanaya, B. Gable, P. A. Murray and D. S. Damron, “Propofol Increases Phosphorylation of Troponin 1 and Myosin Light Chain via Protein Kinase C Activation in Cardiomyocytes,” Anesthesiology, Vol. 98, No. 6, 2003, pp. 1363-1371.
[8] M. Horibe, I. Kondo, D. S. Damron and P. A. Murray, “Propofol Attenuates Capacitatine Calcium Entry in Pul- monary Artery Smooth Muscle Cells,” Anesthesiology, Vol. 95, No. 3, 2001, pp. 681-688.
[9] N. Kanaya, P. A. Murray and D. S. Damron, “Propofol Increases Ca2+ Sensitivity and Intracellular pH via Activation of Na+ -H+ Exchange in Rat Ventricular Myocytes,” Anesthesiology, Vol. 94, No. 6, 2001, pp. 1096- 1104.
[10] Y. Shin, S. Urano and T. Endo, “Antioxidant Property of Propofol and Related Monomeric and Dimeric Compounds,” Chemical and Pharmaceutical Bulletin, Vol. 53, No. 3, 2005, pp. 344-346.
[11] P. E. Marik, “Propofol Therapeutic Indications and Side- Effects,” Current Pharmaceutical Design, Vol. 10, No. 29, 2004, pp. 3639-3649.
[12] V. Ioanna, X. Theodoros, K. Eleni, P. Despoina, K. Chris, K. Athanasius and P. Lila, “Propofol: A Review of its Non-Anesthetic Effects,” European Journal of Pharmacology, Vol. 605, No. 1-3, 2009, pp. 1-8.
[13] T. Mammoto, M. Mukai, A. Mammoto, Y. Yamanaka, Y. Hayashi, T. Mashimo, Y. Kishi and H. Nakamura, “Intravenous Anesthetic, Propofol Inhibits Invasion of Cancer Cells,” Cancer Letter, Vol. 184, No. 2, 2002, pp. 165- 170.
[14] K. Atsuko, I. Takefumi and S. Koh, “Enhancement of Anti-Tumor Immunity after Propofol Treatment in Mice,” Immuno Pharmacology and Immunotoxicology, Vol. 29, No. 3-4, 2004, pp. 477-486.
[15] R. A. Siddiqui, M. Zerouga, M. Wu, A. Castillo, K. Harvey, G. P. Zaloga and W. Stillwell, “Anti-Cancer Properties of Propofol-Docosahexaenoate and Propofoleicosa- pentaenoate on Breast Cancer Cells,” Breast Cancer Research, Vol. 7, No. 5, 2005, pp. 645-654.
[16] K. A. Harvey, Z. Xu, P. Whitley, V. J. Davisson and R. A. Siddiqui, “Characterization of Anti-Cancer Properties of 2,6-Diisopropylphenoldocosahexaenoate and Analogues in Breast Cancer Cells,” Bioorganic and Medicinal Che- mistry, Vol. 18, No. 5, 2010, pp. 1866-1874.
[17] J. A. Monendez, S. Ropero, R. Lupu and R. Colomer, “n-6 PUFA γ-Linolenic Acid (18: 3n-6) Enhances Docetaxel (Taxotere) Cytotoxicity in Human Breast Carcinoma Expression,” Oncology Reports, Vol. 11, No. 6, 2004, pp. 1241-1252.
[18] M. P. Moyer, W. E. Hardman and I. Canceron, “Accelerated Action Fatty Acid (AAFA) Promotes Health of Normal Tissues and Minimizes the Toxic Side Effects of Chemotherapy,” U.S. Patent, 102907, 2002.
[19] W. E. Hardman, I. L. Cameron and M. P. Moyer, “Fatty Acids to Minimize Cancer Therapy Side Effects,” PCT International, WO-US16666 0722, 1999.
[20] S. C. Larsson, M. Kumlin, M. Ingelman-Sundberg and A. Wolk, “Dietary Longchain n-3 Fatty Acids for the Prevention of Cancer: A Review of Potential Mechanisms,” American Journal of Clinical Nutrition, Vol. 79, No. 6, 2004, pp. 935-945.
[21] K. A. Conklin, “Dietary PUFA: Impact on Cancer Chemotherapy and Radiation,” Alternative Medicine Review: A Journal of Clinical Therapeutic, Vol. 7, No. 1, 2002, pp. 4-21.
[22] P. Bougnoux, “n-3 PUFAs and Cancer,” Current Opinion in Clinical Nutrition and Metabolic Care, Vol. 2, No. 2, 1999, pp. 121-126.
[23] R. Berge, “Fatty Acid Analogues for the Treatment of Cancer,” PCT International, WO-NO301 20010713, 2001.
[24] S. Pawar and S. Chattopadhyay, “10-Undecenoic Acid an Inexpensive Source for the Synthesis of the Pheromones of Cotton Pests, Peach Tree Borer and Cherry Tree Borer,” Molecules, Vol. 2, No. 6, 1997, pp. 87-90.
[25] L. Shapiro and S. Rothman, “Undecylenic Acid in the Treatment of Dermatomycoses,” Archives of Dermatology and Syphilology, Vol. 52, No. 3, 1945, pp. 166-171.
[26] N. Mc Lain, R. Ascanio and C. Baker, “Undecylenic Acid Inhibits Morphogenesis of Candida Albicans,” Antimicrobial Agents and Chemotherapy, Vol. 44, No. 10, 2000, pp. 2873-2875.
[27] L. P. Ereaux and G. E. Craig, “Undecylenic Acid in Psoriasis,” Canadian Medical Association Journal, Vol. 61, No. 4, 1949, pp. 361-364.
[28] N. Bourne, J. Ireland, L. R. Stanberry and D. I. Bemstein, “Effect of Undecylenic Acid as a Topical Microbicide against Geniotal Herpes Infection in Mice and Guinea Pigs,” Antiviral Research, Vol. 40, No. 3, 1999, pp. 139- 144.
[29] S. D. Shafran, S. L. Sacks and F. Y. Aoki, “Topical Undecylenic Acid for Herpes Simplex Labiatus: A Multicenter, Placebo-Controlled Trial,” Journal of Infectious Diseases Infect Diseases, Vol. 176, No. 1, 1997, pp. 78-83.
[30] V. P. M. Rahman, S. Mukhtar, W. H. Ansari and G. Lemiere, “Synthesis, Stereochemistry and Biological Activity of Some Novel Long Chain Substituted Thiazolidin- 4-Ones and Thiazan-4-One from 10-Undecenoic Acid Hydrazide,” European Journal of Medicinal Chemistry, Vol. 40, No. 4, 2005, pp. 173-184.
[31] T. Yutaka, K. Masaru, R. Takao, Y. Shusaku and Y. Kenji, “Enzymatic Synthesis of Arbutin Undecylenic Acid Ester and its Inhibitory Effect on Melanin Synthesis,” Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 15, 2007, pp. 894-960.
[32] J. Mustafa, S. I. Khan, G. Ma, L. A. Walker and I. A. Khan, “Synthesis, Spectroscopic and Biological Studies of Novel Estolides Derived from Anti-Tumor Active 4-O-Podophyllotoximyl 12-Hydroxyl Octadec-Z-9 Eno- ate,” Lipids, Vol. 39, No. 6, 2005, pp. 659-666.
[33] P. R. Roper and B. Drewinko, “Comparision of in Vitro Methods to Determine Drug Induced Cell Lethality,” Cancer Research, Vol. 36, No. 7, 1976, pp. 2182-2188.
[34] K. J. Tronstad, K. Berge, R. K. Berge and O. Bruserud, “Modified Fatty Acids and their Possible Therapeutic Targets in Malignant Diseases,” Expert Opinion on Therapeutic Targets, Vol. 7, No. 5, 2003, pp. 663-677.
[35] J. Mustafa, S. I. Khan, G. Ma, L. A. Walker and I. A. Khan, “Synthesis and Anticancer Activities of FA Analogs of Podophyllotoxin,” Lipids, Vol. 39, No. 2, 2004, pp. 167-172.

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