类视黄醇内酯作为皮肤科局部治疗药物的评估。
Evaluation of retinoid lactones as topical therapeutic agents in dermatology.
作者信息
Lewin A H, Black S L, Bos M E, Goehring R R, Nair X, Whiting G, Bouquin P, Tetrault G, Carroll F I
机构信息
Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA.
出版信息
Pharm Res. 1995 Jul;12(7):983-92. doi: 10.1023/a:1016250129246.
PURPOSE
Optimization of the therapeutic ratio of analogs of the topically active 11-cis, 13-cis-12-hydroxymethylretinoic acid, delta-lactone (1) relative to antihyperproliferation and antihyperkeratinization vs. toxicity.
METHODS
Nine analogs of 1, in which variations were made in the lipophilic cyclohexenyl moiety or in the lactone ring, were evaluated for topical activity against hyperkeratinization, inhibition of TPA-induced DNA synthesis and for skin irritation.
RESULTS
Although more potent lactones than the parent lactone 1 were identified, none possessed the favorable therapeutic ratio associated with 1.
CONCLUSIONS
The delta-lactone 1 possesses unique molecular features responsible for its desirable therapeutic ratio as an antihyperproliferative and antihyperkeratotic agent. In view of its very low systemic retinoid toxicity and the absence of any systemic toxicity, this lactone may be a good candidate for use in the topical treatment of acne.
目的
优化局部活性的11-顺式、13-顺式-12-羟甲基维甲酸δ-内酯（1）类似物相对于抗增殖和抗角化过度与毒性的治疗比率。
方法
评估了1的九种类似物，这些类似物在亲脂性环己烯基部分或内酯环上进行了变化，评估其对角化过度的局部活性、对佛波酯（TPA）诱导的DNA合成的抑制作用以及对皮肤的刺激性。
结果
虽然鉴定出了比母体内酯1更有效的内酯，但没有一种具有与1相关的良好治疗比率。
结论
δ-内酯1具有独特的分子特征，使其作为抗增殖和抗角化过度剂具有理想的治疗比率。鉴于其极低的全身类视黄醇毒性且无任何全身毒性，这种内酯可能是用于痤疮局部治疗的良好候选药物。
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