Enhancing and suppressive effects of immunosuppressants cyclosporin A, FK506, and KM2210 on the colony formation of murine bone marrow cells

Abstract

Immunosuppressants cyclosporin A (CsA), FK506, and KM2210 modulated colony formations of murine hematopoietic progenitor cells. In a 4-h treatment with CsA, 10 micrograms/ml increased the formation of colony-forming units of mixed lineages (CFU-Mix) but decreased the formation of highly proliferative potential colony-forming units (CFU-HPP); 1 microgram/ml of CsA increased the formations of CFU-HPP, CFU-Mix, and colony-forming units of granulocytes/macrophages (CFU-GM); 0.1 microgram of CsA increased the formation of CFU-Mix and burst-forming units of erythroid lineage (BFU-E). Lower doses of CsA appeared to induce an increase in various colony formations. FK506 increased CFU-HPP and CFU-Mix formations at lower doses. Another immunosuppressant, KM2210, increased CFU-HPP and CFU-GM formations but decreased CFU-Mix and BFU-E formations. In a 24-h treatment, 10 micrograms/ml and 1 microgram/ml of CsA inhibited all the colony formations, but 0.1 microgram/ml of CsA increased CFU-Mix, CFU-GM, and BFU-E formations. Similarly, 100 ng/ml and 10 ng/ml of FK506 decreased all the colony formations but 1 ng/ml of FK506 increased CFU-HPP and CFU-GM formations. KM2210 inhibited all the colony formations. These findings showed that lower doses of CsA and FK506 appeared to increase the colony formations, although higher doses of these drugs decreased the colony formations, similar to the findings in a 4-h treatment. On the other hand, KM2210 showed opposing effects on colony formation with 4-h and 24-h treatments.

Total Synthesis and Biological Evaluation of Glycolipids Plakosides A, B and Their Analogs

“…layer was dried (MgSO 4 ) and concentrated in vacuo to give the crude product as a faintly yellow liquid. The crude product was then purified by FC (silica gel; 10% AcOEt in hexanes) to afford 23 ( [(1R,2S)-2-Decylcyclopropyl]methanol (25). To a mixture of dioxaborolane 24 (18.77 g, 62.92 mmol), 23 (10.40 g, 52.44 mmol), and activated 4-molecular sieves (2.00 g) in CH 2 Cl 2 at À 158 was dropwise added a freshly prepared soln.…”

“…The IC 50 values of the reference compounds cyclosporine A (CsA) [25], a T-cell-selective immunosuppressant, and azathioprine [26], a nucleotide analogue, which interferes with DNA synthesis and thus generally inhibits cell proliferation, are shown in the Table. CsA showed a T-cell-selective activity profile; it inhibited the MLR and the Con A response Scheme 6. Synthesis of Plakoside Analogs 2 ± 4 and 7 ± 9 a) DIBAL (1.5 equiv.…”