Holographic Quantitative Structure-Toxicity Relationships on the Skin Sensitization of Alkyl-3,4- dihydroxybenzoate and N-Alkyl -3,4- dihydroxybenzamide Derivatives

Holographic quantitative structure-toxicity relationships (HQSTR) of alkyl-3,4-dihydroxybenzoate (A) and N-alkyl-3,4-dihydroxybenzamide (B) derivatives were analyzed and discussed. The HQSTR model X for the skin sensitivity showed the best predictability based on the cross-validated $r^2_{cv}.$ ($q^2 = 0.744$), non cross-validated, and conventional coefficient ($r^2_{ncv}.$=0.978). The relationships between melanogenesis inhibitory activities and skin sensitization of compounds have a tendency to a reciprocal proportion. Therefore, the more higher melanogenesis inhibitory activities of compounds were, the more lower skin sensitization of compounds became. The side chain, C1 ${\~}$ C3 part of R1-substituents in (A) and (B) did not exhibit any contribution to skin sensitization. Particularly, it is reveals that the skin sensitization of ester (A) were slightly lower (A < B) than that of amide (B) and melanogenesis Inhibitory activities of (A) were slightly higher (A > B) than that of (B). It is founded that the alkyl-3,4-dihydroxybenzoate derivatives (A) were an ideal compound as an ingredient of whitening agents.

Alkyl-3,4-dihydroxybenzoate와 N-Alkyl-3,4-dihydroxybenzamide 유도체의 피부 감작성에 관한 홀로그래피적인 정량적 구조와 독성과의 관계(HQSTR)

일련의 alkyl-3,4-dihydroxybenzoate (A)와 N-alkyl-3,4-dihydroxybenzamide (B) 유도체들의 치환기(R1 및 R2) 변화에 따른 피부 감작성과의 관계를 HQSTR 방법으로 분석하였다. 유도된 피부 감작성에 관한 HQSTR 모델은 매우 양호한 예측성(cross-validated $r^2_{cv}.,\;q^2=0.744$)과 적합성(non-cross-validated, $r^2_{ncv}$. =0.978)을 나타내었다. 이들 두 화합물은 멜라닌 생성 저해 활성이 클수록 피부 감작성이 낮은 반비례적인 경향을 보였으며 R1-치환기 사슬 중 C1 ${\~}$ C3 원자 부분은 피부 감작성에 기여하지 않는 경향을 나타내었다. 따라서 ester (A)는 amide (B)보다 피부 감작성이 낮으나(AB) 특징을 나타내므로 미백제의 활성 성분으로서 매우 이상적인 화합물임을 알았다.