Anti-HIV-1 integrase compounds from Dioscorea bulbifera and molecular docking study

Abstract

Context Dioscorea bulbifera L. (Dioscoreaceae) has been used in a traditional Thai longevity medicine preparation. Isolation of inhibitors from natural products is a potential source for continuous development of new HIV-1 integrase (IN) inhibitors. Objective The objective of this study is to isolate the compounds and evaluate their anti-HIV-1 IN activity, as well as to predict the potential interactions of the compounds with an IN. Materials and methods The ethyl acetate and water fractions (1-100 mg/mL) of Dioscorea bulbifera bulbils were isolated and tested for their anti-HIV-1 IN activity using the multiplate integration assay (MIA). The interactions of the active compounds with IN were investigated using a molecular docking method. Results and discussions The ethyl acetate and water fractions of Dioscorea bulbifera bulbils afforded seven compounds. Among these, allantoin (1), 2,4,3 0 ,5 0 -tetrahydroxybibenzyl (2), and 5,7,4 0 -trihydroxy-2-styrylchromone (5) were isolated for the first time from this plant. Myricetin (4) exhibited the most potent activity with an IC 50 value of 3.15 mM, followed by 2,4,6,7-tetrahydroxy-9,10-dihydrophenanthrene (3, IC 50 value¼ 14.20 mM), quercetin-3-O-b-D-glucopyranoside (6, IC 50 value ¼ 19.39 mM) and quercetin-3-O-b-D-galactopyranoside (7, IC 50 value ¼ 21.80 mM). Potential interactions of the active compounds (3, 4, 6, and 7) with the IN active site were additionally investigated. Compound 4 showed the best binding affinity to IN and formed strong interactions with various amino acid residues. These compounds interacted with Asp64, Thr66, His67, Glu92, Asp116, Gln148, Glu152, Asn155, and Lys159, which are involved in both the 3 0 -processing and strand transfer reactions of IN. In particular, galloyl, catechol, and sugar moieties were successful inhibitors for HIV-1 IN.ARTICLE HISTORY

Docking Studies of HIV-1 Reverse Transcriptase and HIV-1 Integrase with Phytocompounds of Carissa Carandas L.

“…HIV-1 integrase [34] and reported the significant anti-HIV activity of phytochemicals. In-silico analysis of Dolichin A and B against HIV-RT was also evaluated [35].…”

Quantitative Structure–Cytotoxicity Relationship of 2-Styrylchromones

“…The difference (T-N) was used as a tumor-specificity index in the following analyses (21). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] investigated in this study. Hungary) (23), was optimized by CORINA Classic (Molecular Networks GmbH, Germany) with forcefield calculations (amber-10: EHT) in Molecular Operating Environment (MOE) version 2018.0101 (Chemical Computing Group Inc., Quebec, Canada) (24).…”

“…Synthesis of test compounds. 2-[(1E)-2-Phenylethenyl]-4H-1benzopyran-4-one [1], 2-[(1E)-2-(4-fluorophenyl)ethenyl]-4H-1benzopyran-4-one [2], 2-[(1E)-2-(4-chlorophenyl)ethenyl]-4H-1benzopyran-4-one [3], 2-[(1E)-2-(4-bromophenyl)ethenyl]-4H-1benzopyran-4-one [4], 2-[(1E)-2-(4-methoxyphenyl)ethenyl]-4H-1benzopyran-4-one [5], 2-[(1E)-2-(3,4-dimethoxy)ethenyl]-4H-1benzopyran-4-one [6], 6-methoxy-2-[(1E)-2-phenylethenyl]-4H-1benzopyran-4-one [7], 2-[(1E)-2-(4-fluorophenyl)ethenyl]-6-methoxy-4H-1-benzopyran-4-one [8], 2-[(1E)-2-(4-chlorophenyl)ethenyl]-6methoxy-4H-1-benzopyran-4-one [9], 2-[(1E)-2-(4-bromophenyl) ethenyl]-6-methoxy-4H-1-benzopyran-4-one [10], 6-methoxy-2-[(1E)-2-(4-methoxyphenyl)ethenyl]-4H-1-benzopyran-4-one [11], 2-[(1E)-2-(3,4-dimethoxy)ethenyl]-6-methoxy-4H-1-benzopyran-4-one [12], 7methoxy-2-[(1E)-2-phenylethenyl]-4H-1-benzopyran-4-one [13], 2-[(1E)-2-(4-fluorophenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one [14], 2-[(1E)-2-(4-chlorophenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one [15], 2-[(1E)-2-(4-bromophenyl)ethenyl]-7-methoxy-4H-1-benzopyran-4-one [16], 7-methoxy-2-[(1E)-2-(4-methoxyphenyl) ethenyl]-4H-1-benzopyran-4-one [17], and 2-[(1E)-2-(3,4-dimethoxy) ethenyl]-7-methoxy-4H-1-benzopyran-4-one [18] were synthesized by the condensation of the corresponding 2-methylchromones with selected benzaldehyde derivatives, according to previous methods (19). All compounds were dissolved in DMSO at 40 mM and stored at -20˚C before use.…”

An Overview of 2‐Styrylchromones: Natural Occurrence, Synthesis, Reactivity and Biological Properties

“…The configuration and conformation of 2-SCs were established through the analysis of their 1D and 2D NMR spectra. The vicinal coupling constant (J Hα,H ) at about [15][16][17] Hz indicates a trans configuration for the double bond in all known natural 2-SC derivatives and almost all the synthetic derivatives. [5][6][7] In addition, NOE cross peaks observed between H-α and H-3 and the absence of cross peaks between H-and H-3 confirm that, in solution, parent 2-SC (1) exists in a C2-Cα s-trans conformation.…”

“…[15] Meanwhile, derivative 6 has also been isolated from heartwood of Juniperus chinensis (by heating at reflux in methanol) [16] and from an ethanol extract of the bulbils of Dioscorea bulbifera. [17] It is also worth noting that compound 6 was synthesized by us prior to its isolation. [18] Of compounds 7-10, named platachromones A-D, the prenylated analogue platachromone B (8) has recently been synthesized by our group.…”