Current immunosuppressive agents: efficacy, side effects, and utilization

Smith, Jodi M.; Nemeth, Thomas L.; McDonald, Ruth A.

doi:10.1016/s0031-3955(03)00121-4

Cited by 85 publications

(55 citation statements)

References 68 publications

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“…Intermediate 13, in turn, was to be prepared through a [2,3]-Wittig rearrangement of the stannyl methyl ether 14, which is accessible from the known trans-decalone 15. [6][7][8]10] Synthesis of decalin segment 12: The synthesis of 12, starting from the known trans-decalone 15 [6][7][8]10] (Ͼ 99 % ee), is shown in Scheme 2; the route is based on our pre-vious work.…”

Section: Resultsmentioning

confidence: 99%

“…[2] Thus, there exists a clear need for the identification and development of new immunosuppressive agents with high efficacy and low toxicity. [1][2][3] In 1995, Strobel and Clardy et al reported the isolation and structural elucidation of two novel immunosuppressive, but non-cytotoxic, diterpenoid pyrones subglutinols A and B (1 and 2, Figure 1) from the endophytic fungus Fusarium subglutinans. [4] It has been reported that the immunosuppressive activity of 1 and 2 is comparable; they were found to be equipotent in the mixed lymphocyte reaction (MLR) assay (IC 50 = 0.1 μm) and the thymocyte proliferation (TP) assay (IC 50 = 0.1 μm).…”

Section: Introductionmentioning

confidence: 99%

“…Figure 2. Structures of sesquicillin (3), nalanthalide (4), and candelalides A (5), B (6), and C (7).…”

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confidence: 99%

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Enantioselective Total Synthesis of (–)‐Subglutinols A and B: Potential Immunosuppressive Agents Isolated from a Microorganism

et al. 2011

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Potential immunosuppressive diterpenoid pyrones (–)‐subglutinols A and B were efficiently synthesized in an enantioselective manner starting from a known trans‐decalone derivative. The synthetic method involved the following key steps: (i) [2,3]‐Wittig rearrangement of a stannyl methyl ether to access the requisite decalin segment; (ii) coupling of the decalin segment with a γ‐pyrone moiety to set up the desired carbon framework; (iii) construction of a characteristic tetrahydrofuran ring in one‐pot fashion through an internal SN2‐type cyclization, and (iv) conversion of a γ‐pyrone moiety into an α‐pyrone ring to yield the target (–)‐subglutinols A and B.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enantioselective Total Synthesis of (–)‐Subglutinols A and B: Potential Immunosuppressive Agents Isolated from a Microorganism

et al. 2011

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“…[3] Although immunosuppressive drugs have been successfully used for organ transplantation and treatment of autoimmune diseases in the clinic, their side effects cannot be neglected. [4][5][6][7][8][9] Therefore, there is a clinical need for new therapeutic agents capable of modulating immune responses with high efficacy and low toxicity.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Immunosuppressive Activity of New Deoxybenzoin Derivatives

Luo

Song

et al. 2010

ChemMedChem

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In the search for potential immunosuppressive agents with high efficacy and low toxicity, a series of new deoxybenzoins were synthesized and evaluated for their cytotoxicity and immunosuppressive activity. Among the synthesized compounds, four deoxybenzoin oximes (compounds 31, 32, 37, and 38) exhibited lower cytotoxicity and higher inhibitory activity toward anti-CD3/anti-CD28 co-stimulated T-cell proliferation than other compounds. More significantly, compound 31 is >100-fold less cytotoxic than cyclosporine A (CsA) and is also more potent (31: SI>684.64, CsA: SI=235.44). The preliminary inhibition mechanism of compound 31 was also identified by flow cytometry, and this compound exerts immunosuppressive activity by inducing apoptosis in activated lymph node cells in a dose-dependent manner. In addition, the mechanism of apoptosis was detected by western blot analysis.

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“…The most extensively used immunosuppressive drugs are cyclosporine A (CsA), tacrolimus, and sirolimus (Smith et al, 2003). All these drugs affect not only the cells of the immune system, but have some adverse functions on other cells or tissues (Saeed et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Colchicine-derived compound CT20126 promotes skin allograft survival by regulating the balance of Th1 and Th2 cytokine production

Lee¹,

Namkoong²,

Ha³

et al. 2007

Exp Mol Med

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Colchicine has been shown to regulate the expression of inflammatory gene, but this compound possesses much weaker anti-inflammatory activity. In this study, we synthesized a new colchicine derivative CT20126 and examined its immunomodulatory property. CT20126 was found to have immunosuppressive effects by inhibiting lymphocyte proliferation without cytotoxicity and effectively inhibit the transcriptional expression of the inflammatory genes, iNOS, TNF-α, and IL-1β, in macrophages stimulated by LPS. This effect was nearly comparable to that of cyclosporine A. This compound also significantly suppressed the production of nitric oxide and Th1-related pro-inflammatory cytokines, IL-1β, TNF-α, and IL-2, with minimal suppression of Th2-related anti-inflammatory cytokines IL-4 and IL-10 in the sponge matrix allograft model. Moreover, administration of CT20126 prolonged the survival of allograft skins from BALB/c mice (H-2 d ) to the dorsum of C57BL/6 (H-2 b ) mice. The in vivo immune suppressive effects of CT20126 were similar to that of cyclosporine A. These results indicate that this compound may have potential therapeutic value for transplantation rejection and other inflammatory diseases.

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Current immunosuppressive agents: efficacy, side effects, and utilization

Cited by 85 publications

References 68 publications

Enantioselective Total Synthesis of (–)‐Subglutinols A and B: Potential Immunosuppressive Agents Isolated from a Microorganism

Enantioselective Total Synthesis of (–)‐Subglutinols A and B: Potential Immunosuppressive Agents Isolated from a Microorganism

Design, Synthesis, and Immunosuppressive Activity of New Deoxybenzoin Derivatives

Colchicine-derived compound CT20126 promotes skin allograft survival by regulating the balance of Th1 and Th2 cytokine production

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