The supramolecular structure of 6-hydroxy-1,3-benzoxathiol-2-one (tioxolone)

Byres, Maureen; Cox, Philip

doi:10.1107/s0108270104008236

Cited by 4 publications

(9 citation statements)

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“…All 16 analogues contained the original thioxolone ring structure, but also had additional aliphatic and aromatic groups substituted at the C6 carbon hydroxyl group, using the nomenclature of Byres and Cox (53). Some analogues were also modified by halogenation of the C1 and/or C5 carbons.…”

Section: X-ray Crystallography Of Thioxolone Compounds Withmentioning

confidence: 99%

“…Other reported medically useful properties include cytostatic, (56) antipsoriatic, antibacterial, and antimycotic activity; (54) some toxicity issues involving contact dermatitis have also been reported for this compound (57). The thioxolone structure is somewhat polar, with an XlogP value of 1.3, and has one hydrogen bond donor (a hydroxyl group) on one end and three hydrogen bond acceptors, including a carbonyl group on the other end, allowing for the formation of extensive hydrogen bonds (53). This structure lacks sulfonamide, sulfamate, or related functional groups that are typically a key structural feature of known CA inhibitors (39).…”

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confidence: 99%

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Inhibition of Carbonic Anhydrase II by Thioxolone: A Mechanistic and Structural Study

et al. 2008

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This paper examines the functional mechanism of thioxolone, a compound recently identified as a weak inhibitor of human carbonic anhydrase II by Iyer et al. (2006) J. Biomol. Screening 11, 782-791. Thioxolone lacks sulfonamide, sulfamate, or hydroxamate functional groups that are typically found in therapeutic carbonic anhydrase (CA) inhibitors, such as acetazolamide. Analytical chemistry and biochemical methods were used to investigate the fate of thioxolone upon binding to CA II, including Michaelis-Menten kinetics of 4-nitrophenyl acetate esterase cleavage, liquid chromatography-mass spectrometry (LC-MS), oxygen-18 isotope exchange studies, and X-ray crystallography. Thioxolone is proposed to be a prodrug inhibitor that is cleaved via a CA II zinc-hydroxide mechanism known to catalyze the hydrolysis of esters. When thioxolone binds in the active site of CA II, it is cleaved and forms 4-mercaptobenzene-1,3-diol via the intermediate S- (2,4-thiophenyl)hydrogen thiocarbonate. The esterase cleavage product binds to the zinc active site via the thiol group and is therefore the active CA inhibitor, while the intermediate is located at the rim of the active-site cavity. The time-dependence of this inhibition reaction was investigated in detail. Because this type of prodrug inhibitor mechanism depends on cleavage of ester bonds, this class of inhibitors may have advantages over sulfonamides in determining isozyme specificity. A preliminary structure-activity relationship study with a series of structural analogues of thioxolone yielded similar estimates of inhibition constants for most compounds, although two compounds with bromine groups at the C1 carbon of thioxolone were not inhibitory, suggesting a possible steric effect.

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Section: X-ray Crystallography Of Thioxolone Compounds Withmentioning

confidence: 99%

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confidence: 99%

Inhibition of Carbonic Anhydrase II by Thioxolone: A Mechanistic and Structural Study

et al. 2008

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“…Only M. Byres et al presented the supramolecular structure of tioxolone [6], and no corresponding vibrational properties of tioxolone has been published yet. This motivates us to make an in-depth theoretical study on tioxolone.…”

Section: Introductionmentioning

confidence: 95%

“…Therefore, it is widely used in various combination drugs for treating acne and psoriasis [4]. For example, some haircare products have incorporated tioxolone into their formulation as an antiseborrheic agent due to its oil-regulating and antibacterial properties [5,6]. Because of containing ester and thioester group, tioxolone is also applied in the synthesis of heterocycle-phosphor esters with potential antimicrobial activity.…”

Section: Introductionmentioning

confidence: 99%

Spectroscopy (FT-IR, FT-Raman), hydrogen bonding, electrostatic potential and HOMO-LUMO analysis of tioxolone based on DFT calculations

Tao

Han

et al. 2016

Journal of Molecular Structure

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“…5), (II) ( Fig. 6) and tioxolone (refcode: EVOQEL), which features classical O-HÁ Á ÁO hydrogen bonds (Byres & Cox, 2004) (Fig. 7) were calculated with CrystalExplorer17 (Turner et al, 2017).…”

Section: Hirshfeld Analysesmentioning

confidence: 99%

Crystal structures and Hirshfeld surfaces of two 1,3-benzoxathiol-2-one derivatives

et al. 2018

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The crystal structures of 6-methoxy-1,3-benzoxathiol-2-one, C 9 H 8 O 3 S, (I), and 2-oxo-1,3-benzoxathiol-6-yl acetate, C 9 H 6 O 4 S, (II), are described. Compound (I) is almost planar (r.m.s. deviation for the non-H atoms = 0.011 Å ), whereas (II) shows a substantial twist between the fused-ring system and the acetate substituent [dihedral angle = 74.42 (3) ]. For both structures, the bond distances in the heterocyclic ring suggest that little if any conjugation occurs. In the crystal of (I), C-HÁ Á ÁO hydrogen bonds link the molecules into [111] chains incorporating alternating R 2 2 (8) and R 2 2 (12) inversion dimers. The extended structure of (II) features C(7) [201] chains linked by C-HÁ Á ÁO hydrogen bonds, with further C-HÁ Á ÁO bonds and weak -stacking interactions connecting the chains into a three-dimensional network. Hirshfeld fingerprint analyses for (I) and (II) are presented and discussed. Chemical context1,3-Benzoxathiol-2-one and its derivatives have various biological properties including antibacterial, antimycotic, antioxidant, antitumor and anti-inflammatory activities (Vellasco Jú nior et al., 2011;Chazin et al., 2015). They also act as inhibitors of carbonic anhydrase II (Barrese et al., 2008) and monoamine oxidase (Mostert et al., 2016). The first synthesized 1,3-benzoxathiol-2-one, 6-hydroxy-1,3-benzoxathiol-2-one C 7 H 4 O 3 S, also known as tioxolone or thioxolone, has been used for many years in the treatment of acne and other skin diseases (e.g. psoriasis) (Berg & Fiedler, 1959).A recent study reported the syntheses and antifungal activities of some derivatives of tioxolone (Terra et al., 2018). In the present article we report the crystal structures and Hirshfeld surface analyses of two compounds with different substituents at the 6-position of the ring system obtained in that study, viz. 6-methoxy-1,3-benzoxathiol-2-one, C 9 H 8 O 3 S, (I), and 2-oxo-1,3-benzoxathiol-6-yl acetate, C 9 H 8 O 3 S, (II).. ISSN 2056-9890 Structural commentaryCompound (I) crystallizes in space group P1 with one molecule in the asymmetric unit (Fig. 1), which is almost planar (r.m.s. deviation for the non-hydrogen atoms = 0.011 Å ): the ethoxy side chain adopts an extended conformation [C6-O3-C8-C9 = 179.82 (12) ]. Within the oxathiol-2-one ring system, the C1-O1, C1 O2 and C1-S1 bond lengths are 1.3732 (18), 1.1905 (19) and 1.7766 (16)Å , respectively, and the O1-C1-S1 and C1-S1-C3 bond angles are 111.07 (11) and 90.62 (7) , respectively. These distance data suggest that there is little if any conjugation (i.e. partial double-bond character) involving the C1-O1 and C1-S1 bonds with the C1 O2 group.A single molecule of compound (II) makes up the asymmetric unit in space group P2 1 /c (Fig. 2). The ring system is almost planar (r.m.s. deviation for C1-C7/O1/S1 = 0.032 Å ) but there is a substantial twist about the C6-O3 bond, as indicated by the dihedral angle between the ring system and the acetate group of 74.42 (3) . Key geometrical data for the heterocyclic ring are C1-O1 = 1.3864 (15), C1 ...

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The supramolecular structure of 6-hydroxy-1,3-benzoxathiol-2-one (tioxolone)

Abstract: The planar molecules of 6-hydroxy-1,3-benzoxathiol-2-one, C(7)H(4)O(3)S, are linked by extensive O-H.O and C-H.O hydrogen bonding and are further stablilized by face-to-face pi-pi interactions.

Cited by 4 publications

References 6 publications

Inhibition of Carbonic Anhydrase II by Thioxolone: A Mechanistic and Structural Study

Inhibition of Carbonic Anhydrase II by Thioxolone: A Mechanistic and Structural Study

Spectroscopy (FT-IR, FT-Raman), hydrogen bonding, electrostatic potential and HOMO-LUMO analysis of tioxolone based on DFT calculations

Crystal structures and Hirshfeld surfaces of two 1,3-benzoxathiol-2-one derivatives

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