Med Chem Res
Lonchocarpus xuul Lundell by NO production: Computational
and ex vivo approaches. Phytomedicine 20:1241–1246
Cragg GM, Newman DJ (2013) Natural products: a continuing source
of novel drug leads. Biochim Biophys Acta 1830:3670–3695
Dassault Systèmes BIOVIA (2016) Discovery Studio Modeling
Environment, Release 2017. Dassault Systèmes, San Diego
Ertl P, Rohde B, Selzer P (2000) Fast calculation of molecular polar
surface area as a sum of fragment based contributions and its
application to the prediction of drug transport properties. J Med
Chem 43:3714–3717
Escalante-Erosa F, González-Morales B, Quijano-Quiñiones RF,
Miron-López G, Peña-Rodríguez LM (2012) Dihydro-
spinochalcone-a and epi-flemistrictin-B, natural isocordoin deri-
vatives from the root extract of Lonchocarpus xuul. Nat Prod
Commun 7:1589–1590
Estrada-Soto S, Sánchez-Recillas A, Navarrete-Vázquez G, Castillo-
España P, Villalobos-Molina R, Ibarra-Barajas M (2012) Relax-
ant effects of Artemisia ludoviciana on isolated rat smooth muscle
tissues. J Ethnopharmacol 139:513–518
Gogoi D, Baruah VJ, Chaliha AK, Kakoti BB, Sarma D, Buragohain
AK (2017) Identification of novel human renin inhibitors through
a combined approach of pharmacophore modelling, molecular
DFT analysis and in silico screening. Comput Biol Chem
µ
Fig. 3 Relaxant concentration–response curves of 6-hydroxyflavone
2), comparing with 6-aminoflavone (3) and 6-methoxyflavone (4) on
the carbachol-contracted isolated rat tracheal rings. Each point repre-
sents the mean ± S.E.M. of five experiments
(
(
2) and 6-aminoflavone (3), which demonstrated a sig-
6
9:28–40
Harborne JB, Williams C (2000) Advances in flavonoid research since
992. Phytochemistry 55:481–504
nificant concentration-dependent relaxant effect (Fig. 3).
These latter results indicate that the flavone scaffold is
necessary to present hydrogen-bond donors or acceptors
but, if both proton donors and acceptors exist (such as the
1
Hidalgo-Figueroa S, Navarrete-Vázquez G, Estrada-Soto S, Giles-
Rivas D, Alarcón-Aguilar FJ, León-Rivera I, Giacoman-Martínez
A, Miranda Pérez E, Almanza-Pérez JC (2017) Discovery of new
dual PPARγ-GPR40 agonists with robust antidiabetic activity:
Design, synthesis and in combo drug evaluation. Biomed Phar-
macother 90:53–61
–
OH group) in position -6, activity is improved. Also, the
presence of the hydroxyl group in the -7 position also
preserves relaxant activity in tracheal rat rings. In this
context, 6-hydroxyflavone (2) exhibited significant relaxant
activity in contractions induced by CCh in tracheal rat rings,
which represents a potential prototype for future preclinical
studies in order to develop a novel antiasthmatic drug.
Also, based on the SAR study, we could design and
semi-synthesize compounds employing the proposed
pharmacophore.
Kerns H, Di LE (2015) Lipophilicity. In: Drug like properties: concepts,
structure design and methods from ADME to toxicity optimization,
1
st Ed. Academic Press, Elsevier, New York, p 43–47
Land MH, Wang J (2017) Complementary and alternative medicine
use among allergy practices: results of a nationwide survey of
allergists.
J
Allergy Clin Immunol Pract S2213-2198
(17):30031–30034
Mali RG, Dhake AS (2011) A review on herbal antiasthmatics. Orient
Pharm Exp Med 11:77–90
Mastuda H, Morikawa T, Ueda K, Managi H, Yoshikawa M (2002)
Structural requirements of flavonoids for inhibition of antigen-
Induced degranulation, TNF-alpha and IL-4 production from
RBL-2H3 cells. Bioorg Med Chem 10:3123–3128
Acknowledgements This work was supported in part by Facultad de
Farmacia (UAEM) internal grants, as well as from SEP-CONACyT
Ciencia Básica (grant 167044 and 256197).
Remko M, Swart M, Bickelhaupt FM (2006) Theoretical study of
structure, pKa, lipophilicity, solubility, absorption, and polar
surface area of some centrally acting antihypertensives. Bioorg
Med Chem 14:1715–1728
Compliance with ethical standards
Conflict of interest The authors declare that they have no competing
interests.
Sunhee L, Byoung HM, Younghee P, Eunjung L, Sungwon H, Y L
(2008) Methyl substitution effects on 1H and 13C NMR data of
methoxyflavones. Bull Korean Chem Soc 29:1793–1796
Shrimanker R, Pavord ID (2017) Interleukin-5 inhibitors for severe
asthma: rationale and future outlook. BioDrugs 31:93–103
Tanaka T, Takahashi R (2013) Flavonoids and asthma. Nutrients
References
5
:2128–2143
Taur DJ, Patil RY (2011) Some medicinal plants with antiasthmatic
potential: a current status. Asian Pac J Trop Biomed 1:413–418
Torres-Piedra M, Figueroa M, Hernández-Abreu O, Ibarra-Barajas M,
Navarrete-Vázquez G, Estrada-Soto S (2011) Vasorelaxant effect
of flavonoids through calmodulin inhibition: Ex vivo, in vitro,
and in silico approaches. Bioorg Med Chem 19:542–446
Ajay M, Gilani AH, Mustafa MR (2003) Effects of flavonoids on
vascular smooth muscle of the isolated rat thoracic aorta. Life Sci
7
4:603–612
Ávila-Villareal G, Hernández-Abreu O, Hidalgo-Figueroa S,
Navarrete-Vázquez G, Escalante-Erosa F, Peña-Rodríguez LM,
Villalobos-Molina R, Estrada-Soto S (2013) Antihypertensive
and vasorelaxant effects of dihydrospinochalcone-A isolated from
Yam PA, Peña-Rodríguez LM (2009) Isocordoin derivatives from the
root extract of Lonchocarpus xuul. J Mex Chem Soc 53:12