Curcumin analogues exert potent inhibition on human and rat gonadal 3β-hydroxysteroid dehydrogenases as potential therapeutic agents: structure-activity relationship and in silico docking

Qiao, Xinyi; Ye, Lei; Lu, Jialin; Pan, Chengshuang; Fei, Qianjin; Zhu, Yang; Li, Huitao; Lin, Han Chieh; Ge, Ren‐Shan; Wang, Yiyan

doi:10.1080/14756366.2023.2205052

Cited by 2 publications

(2 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results of higher anti-melanogenic activity of BDC than PC, DC, and THC, with a differential efficacy of BDC in mouse and human cells, are reminiscent of the results of a previous study [71] that demonstrated that BDC emerged as the most potent inhibitor of the activity of the 3β-hydroxysteroid dehydrogenase enzyme compared to THC, PC, and DC, with a differential efficacy across human and rat species. Notably, the two other compounds, THBDC and THDC, were not examined in their study; hence, it remains unknown if THBDC may have been superior to BDC in their assays.…”

Section: Discussionsupporting

confidence: 71%

“…LogP values are a measure of the lipophilicity of a drug and are useful in SAR studies [72]. In the previous study [71], it was also shown that the higher inhibitory effects of BDC were correlated to its lower logP values and, thus, lower lipophilicity, leading the authors to suggest that removing both methoxy groups is expected to increase potency. Our findings of the higher capacity of BDC or THBDC (both demethoxylated) inhibiting tyrosinase activity and melanogenesis can be attributed to the removal of both of their methoxy groups, which enables the hydroxyl groups to form hydrogen bonds more easily with the tyrosinase enzyme, thereby enhancing their inhibitory potency.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Study of the Effects of Curcuminoids and Tetrahydrocurcuminoids on Melanogenesis: Role of the Methoxy Groups

Goenka

2024

Future Pharmacology

View full text Add to dashboard Cite

Curcuminoids are naturally occurring yellow-colored compounds that, when hydrogenated to remove their conjugated double bond, become colorless and are referred to as tetrahydrocurcuminoids. Curcuminoids consist of pure curcumin (PC) in major amounts and demethoxycurcumin (DC) and bisdemethoxycurcumin (BDC) in minor amounts. Tetrahydrocurcuminoids similarly consist mainly of tetrahydrocurcumin (THC), along with minor amounts of tetrahydrodemethoxycurcumin (THDC) and tetrahydrobisdemethoxycurcumin (THBDC). Previous studies have shown the inhibitory effects of PC, DC, and BDC on melanin production, but there are contradictory findings about THC. In addition, there are currently no reports on the effects of THDC and THBDC on melanogenesis. Our previous report described that, in contrast to PC, which suppressed melanin production, THC stimulated melanin production in B16F10 and MNT-1 cells; this effect was ascribed to the loss of the conjugated heptadiene moiety of PC. However, whether this finding can be generalized to the two curcumin derivatives (DC and BDC), such that THDC and THBDC might also stimulate melanogenesis, has not been addressed. Herein, a comparative study of six curcumin derivatives (PC, DC, BDC, THC, THDC, and THBDC) was undertaken to identify their effects on melanogenesis with the goal of elucidating the structure–activity relationships (SARs) focused on assessing the two regions of the parent curcumins’ structure: (i) the hydrogenation of the two double bonds bridging the phenyl rings to the β-diketone moiety, and (ii) the effect of the ortho-methoxy substituent (-OCH3) on the two phenyl rings. To determine the direct effects of the six compounds, antioxidant activity and tyrosinase activity were assessed in cell-free systems before cellular experiments utilizing the B16F10 mouse melanoma cells, MNT-1 human melanoma cells, and primary cells. Evaluations were made on cytotoxicity, melanin concentration, and cellular tyrosinase activity. The results showed that BDC inhibited melanogenesis in B16F10 and MNT-1 cells. However, it was ineffective in primary human melanocytes, while THBDC continued to exhibit anti-melanogenic capacity in normal human melanocytes. Moreover, these findings provide a novel perspective into the role of the methoxy groups of PC on the biological effects of melanogenesis and also confirm that the removal of the conjugated double bonds abolishes the anti-melanogenic capacity of PC and DC only, but not BDC, as THBDC maintained anti-melanogenic activity that was greater than BDC. However, the outcome is contingent upon the specific kind of cell involved. To the best of our knowledge, this work presents novel findings indicating that the anti-melanogenic capacity of the colored BDC is not only intact but enhanced after its hydrogenation as observed in THBDC. The findings show potential for using colorless THBDC as a pharmacological candidate to diminish the increased pigmentation characteristic of skin hyperpigmentation disorders. Future pharmacological therapeutics that incorporate pure THBDC or THBDC-enriched extracts, which retain both a colorless appearance and potent anti-melanogenic activity, can be applied to compounds for anti-melanoma therapeutics where the demand for nontoxic novel molecules is desired for established efficacies.

show abstract

Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 99%