Cyclosporin D

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Background

Cyclosporin D is an immunosuppressive agent [1]. Cyclosporin D (CsD) is an analogue of cyclosporine A with weak immunosuppressive activity. Cyclosporin D has been used as an internal standard for the quantification of cyclosporin A. In human multidrug-resistant ovarian cancer cells, cyclosporin D significantly overcame adriamycin resistance [2]. In lymphocyte, CsD weakly inhibited PHA-, PWM-, and PMA + Ca2+-induced cell proliferation [3]. In mice, CsD inhibited edema in mouse ear and alkaline phosphatase activity in mouse skin induced by TPA by 98% and 88%, respectively. In cytosol of mouse pancreas, CsD inhibited the Ca2+/calmodulin-dependent phosphorylation of the elongation factor 2 (EF-2) and the TPA-induced increase of EF-2 [1]. Cyclosporin D was effective in inhibiting P. falciparum parasite in vitro and P. berghei malaria parasite development in vivo when administered orally [4].

[1]. Gschwendt M, Kittstein W, Marks F. The weak immunosuppressant cyclosporine D as well as the immunologically inactive cyclosporine H are potent inhibitors in vivo of phorbol ester TPA-induced biological effects in mouse skin and of Ca2+/calmodulin dependent EF-2 phosphorylation in vitro. Biochem Biophys Res Commun, 1988, 150(2): 545-551.
[2]. Mizuno K, Furuhashi Y, Misawa T, et al. Modulation of multidrug resistance by immunosuppressive agents: cyclosporin analogues, FK506 and mizoribine. Anticancer Res, 1992, 12(1): 21-25.
[3]. Sadeg N, Pham-Huy C, Rucay P, et al. In vitro and in vivo comparative studies on immunosuppressive properties of cyclosporines A, C, D and metabolites M1, M17 and M21. Immunopharmacol Immunotoxicol, 1993, 15(2-3): 163-177.
[4]. Uadia PO1, Ezeamuzie IC, Ladan MJ, et al. Antimalarial activity of cyclosporins A, C and D. Afr J Med Med Sci, 1994, 23(1): 47-51.