Antagonist activity of N-benzoylated derivatives 11a–16a in rTRPM8 channels (Ca2+ microfluorometry assay). Activation is induced by 100 µM menthol
Compound
R
aTPSA, (A2)
cLogP
IC50 (µM)
95% confidential intervals
1a
NA
49.85
9.88
1.06 ± 1.21
0.72 to 1.55
2a
NA
58.64
7.63
3.06 ± 1.25
2.67 to 3.51
11a
H
75.71
7.01
2.49 ± 1.45
1.10 to 5.66
12a
Ph
75.71
8.90
1.14 ± 1.53
0.46 to 2.80
13a
F
75.71
7.36
2.30 ± 1.29
1.34 to 3.95
14a
OMe
84.94
7.29
3.21 ± 1.30
1.85 to 5.57
15a
OAc
102.01
6.64
9.73 ± 1.28
5.74 to 16.48
16a
N(Me)2
78.95
7.37
2.54 ± 1.33
1.40 to 4.60
AMTB
NA
ND
ND
7.3 ± 1.5
8.82 to 7.85
aCalculated with ChemDraw 22.2.0. TPSA: total polar surface area; IC50: concentration exerting a half-maximal inhibition; rTRPM8: rat transient receptor potential melastatin, subtype 8; R: substituent at the benzoyl moeity; cLogP: logarithm of the partition coefficient between n-octanol and water; ND: no data; NA: not applicable
CME and TV: Investigation, Formal analysis, Writing—review & editing. MAB and AMP: Investigation, Writing—review & editing. AFM: Supervision, Funding acquisition, Writing—review & editing. AFC: Supervision, Funding acquisition, Writing—original draft, Writing—review & editing. RGM: Conceptualization, Supervision, Funding acquisition, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.
Conflicts of interest
Rosario González-Muñiz, the Editorial Board Member of Exploration of Drug Science and Guest Editor of the special issue—Mimicking Nature: Biomimetics as Tools for Diagnosis and Therapeutics, had no involvement in the journal review process of this manuscript. The other authors declare that they have no conflicts of interest.
Ethical approval
Animal experimentation procedures were conducted under the approval of the Institutional Animal and Ethical Committee at UMH (UMH.IDI.AFM.06.20), and approved by the Generalitat Valenciana (2021/VSC/PEA/0089).
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
Most data from this paper are included in this manuscript and the supplementary materials. Additional data could be obtained from the authors upon request.
Funding
This research was funded by FEDER [MCIN/AEI/10.13039/501100011033]; Una manera de hacer Europa [PID2021-126423OB-C21, to AFM and AFC], [PID2021-126423OB-C22, to RGM]; Generalitat Valenciana [PROMETEO/2021/031, to AFM]; CSIC [202180E073, to RGM]; and Comunidad de Madrid [IND2017/BMD7673, to RGM]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
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