The conformational preferences of acylphloroglucinols—a promising class of biologically active compounds

Abstract

Acylphloroglucinols are a broad class of phloroglucinol derivatives characterized by the presence of a COR group, where R is more often an alkyl chain. They are largely present in natural sources and exhibit a variety of biological activities, including antibacterial, antiviral, antifungal, antitumor, antioxidant, and antimalarial. This work reports the results of a systematic conformational study (in vacuo, chloroform, acetonitrile, and water) of a representative number (118) of actual and model acylphloroglucinol structures, considering the most common R chains and investigating conformational preferences and relative energies as well as the influence of specific structural features characterizing significant subsets of compounds. The study aimed at identifying patterns for conformational preferences and at singling out the conformational aspects more closely related to the individuality of different structures, as these are expected to be more closely linked to the differences in the biological activities of different compounds. The results highlight patterns enabling reliable predictions of the conformational preferences of acylphloroglucinol molecules.

An investigation of aromaticity in hydroxybenzenes based on the study of magnetically induced current density

“…The presence of diffuse and polarization functions in the basis set enables a better description of IHBs (see Refs. and references therein). All these conformers had already been proven to correspond to energy minima with all the calculation methods utilized in Ref.…”

Antioxidant and antimalarial properties of butein and homobutein based on their ability to chelate iron (II and III) cations: a DFT study in vacuo and in solution

“…In a similar manner, the para substituted OH group (O4H4) in ring B can interact with neighbouring O3 to form an IHB, here called the second H-bond and denoted as HB2. IHBs are known to stabilise conformations [47][48][49][50][51][52][53][54][55] as well as to influence the biological activities of compounds, such as antioxidant activity [24,25,32,34].…”

Intramolecular Hydrogen Bonding and Conformational Preferences of Arzanol—An Antioxidant Acylphloroglucinol

“…ACPLs [ 6 ] are derivatives of phloroglucinol (1,3,5-trihydroxybenzene) characterised by the presence of a COR group (acyl group), whose sp 2 O can form an intramolecular hydrogen bond (IHB) with one of the two ortho OHs; following a practice introduced in previous works on ACPLs [ 7 , 8 , 9 , 10 , 11 ], this IHB (which is present in nearly all ACPLs) is here termed ‘first IHB’. In arzanol, R is a methyl group; an α-pyrone ring is attached to one position meta to the COR group (C3) and a prenyl chain is attached to the other meta position (C5).…”

“…The computational study of antioxidant ACPLs responds to the known tight relationships between the molecular properties of polyphenolic compounds and their biological activities [ 12 , 13 , 14 ]. The study of the ARZ molecule is also interesting in view of new information on ACPLs, as the fact that the PHL moiety is bonded to a ring of a different nature (PYR) makes ARZ different from the ACPLs considered so far [ 7 , 8 , 9 , 10 , 11 ], including the dimeric ACPLs in which both units are acylphloroglucinol moieties [ 15 ].…”

“…Conformers were calculated in the gas phase and in solution, considering the same three solvents as in the previous studies of ACPLs (chloroform, acetonitrile and water, [ 7 , 8 , 9 , 10 , 11 ]) to enable informative comparisons. These solvents cover the ranges of polarities and H-bonding abilities of the media in which a biologically active molecule may preferably be present within a living organism.…”