Antitubercular and cytotoxic polyoxygenated cyclohexane derivatives from <i>Uvaria grandiflora</i>

Macabeo, Allan Patrick G.; Flores, Angeli Izza G.; Fernández, Raquel Martínez; Budde, Simon; Faderl, Christian; Dahse, Hans‐Martin; Franzblau, Scott G.

doi:10.1080/14786419.2020.1741579

Cited by 14 publications

(15 citation statements)

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“…The antimicrobial activity against tested microbes including Staphylococcus aureus (ATCC29213), Escherichia coli (ATCC25922), and Candida albicans (ATCC 10231) at 10 µg/ml concentration revealed that all the compounds screened did not show inhibitory activity (for information detail; see Table S4). According to literature reports, the crude extracts and pure compounds isolated from various parts of U. grandiflora were examined for several biological activities such as cytotoxic, anti-inflammatory, antioxidant, and antimicrobial activities [6][7][8][9][20][21][22]. To the best our search from SciFinder database, compounds 1-6 have never been investigated for their antioxidant activity.…”

Section: Resultsmentioning

confidence: 99%

“…Various parts of U. grandiflora have long been used in traditional medicines for curing contusion and body tonic therapies and as a cardiotonic [5]. Previous phytochemical studies on the U. grandiflora resulted in the isolation of various types of compounds including polyoxygenated cyclohexene oxides [6], terpenoids [6], aromatic derivatives [7,8] as well as an alkaloid, velutinam [6], and some of which exhibited promising biological activities. For example, zeylenone, a polyoxygenated cyclohexenone derivative isolated from the leaves and roots of U. grandiflora, displayed significant cytotoxic activity in chronic myelogenous leukemia-derived K562 cell line in both in vitro and in vivo assays [9].…”

Section: Introductionmentioning

confidence: 99%

“…Inspired by the ethnomedicinal use of various parts of U. grandiflora as folk medicines and interesting biologically active components reported to be found in its leaves and roots, it is of high interest to further examine other plant parts of the U. grandiflora. In the course of our continuing efforts to search for biologically active substances from this plant [6][7][8][9], we reported herein the isolation and structural iden-tification of phytochemical components from the MeOH extract of twigs of U. grandiflora. It is worth mentioning that there was no prior phytochemical investigation on the twigs of U. grandiflora found in the literatures.…”

Section: Introductionmentioning

confidence: 99%

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Antioxidant and antimicrobial alkaloids isolated from twigs of Uvaria grandiflora Roxb.

Kongkum¹,

Thanasansurapong²,

Surapanich³

et al. 2021

ScienceAsia

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Phytochemical investigation of the MeOH-EtOAc (1:1 v/v) soluble fraction partitioned from the MeOH extract of twigs of Uvaria grandiflora Roxb. led to the isolation of six known compounds including aristolactam AII (1), aristolactam BI (2), velutinam (3), griffithinam (4), isoursuline (5), and sinactine (6). Their structures were determined on the basis of spectroscopic analysis and comparison with the literature data. Described in this work is the first report of isoursuline (5), an azafluorene derivative, and sinactine (6), a tetrahydroepiberberine, being isolated from plants in the Uvaria genus. Antioxidant and antimicrobial activities of some isolated compounds were evaluated. Among screened compounds, velutinam (3) showed antioxidant activity in the DPPH radical scavenging assay.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antioxidant and antimicrobial alkaloids isolated from twigs of Uvaria grandiflora Roxb.

Kongkum¹,

Thanasansurapong²,

Surapanich³

et al. 2021

ScienceAsia

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“…The extracts and compounds of P. ophthalmicus exhibit photosensitizing effects useful in photodynamic therapies [ 13 ]. As part of our growing interest to validate the ethnomedicinal use of Philippine Annonaceae plants [ 14 , 15 , 16 , 17 , 18 , 19 ], we herein report the inhibitory activity of P. ophthalmicus extracts and tetrahydrobisbenzylisoquinoline alkaloids tetrandrine ( 1 ) and limacusine ( 2 ) ( Figure 1 ) against drug resistant bacterial strains in addition to their cyclooxygenase (COX-1 and -2) inhibitory activities. To probe on the (selective) binding affinity and to depict binding mechanism of antimicrobial and COX-2 inhibitory activity, molecular docking studies and all-atom molecular dynamics simulation experiments were performed against bacterial enzymes and ovine COX isoenzymes.…”

Section: Introductionmentioning

confidence: 99%

Antibacterial and COX-2 Inhibitory Tetrahydrobisbenzylisoquinoline Alkaloids from the Philippine Medicinal Plant Phaeanthus ophthalmicus

Magpantay

Malaluan

Manzano

et al. 2021

Plants

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Phaeanthus ophthalmicus (Roxb. ex G.Don) J.Sinclair (previously known as P. ebracteolatus (Presl) Merr) is a Philippine medicinal plant occurring as evergreen shrub in the lowland forests of Luzon islands. It is used traditionally by Filipinos to treat bacterial conjunctivitis, ulcer and wound infections. Based on previous investigations where cyclooxygenase-2 (COX-2) functions as immune-linked factor in infectious sensitivities to bacterial pathogens by triggering pro-inflammatory immune-associated reactions, we investigated the antimicrobial and COX inhibitory activities of the extracts and tetrahydrobisbenzylisoquinoline alkaloids of P. ophthalmicus in vitro and in silico to validate its ethnomedicinal uses. Thus, the dichloromethane–methanol (DCM–MeOH) crude extract and alkaloid extracts exhibiting antibacterial activities against drug-resistant bacterial strains such as methicillin-resistance Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), Klebsiella pneumoniae + CRE and Pseudomonas aeruginosa + MBL afforded (+)-tetrandrine (1) and (+)-limacusine (2) as the major biologically active tetrahydrobisbenzylisoquinoline alkaloidal constituents after purification. Both tetrahydrobisbenzylisoquinoline alkaloids 1 and 2 showed broad spectrum antibacterial activity with strongest inhibition against the Gram-negative bacteria MβL-Pseudomonas aeruginosa Klebsiella pneumoniae + CRE. Interestingly, the alkaloid limacusine (2) showed selective inhibition against ovine COX-2 in vitro. These results were ascertained by molecular docking and molecular dynamics simulation experiments where alkaloid 2 showed strong affinity in the catalytic sites of Gram-negative bacterial enzymes P. aeruginosa elastase and K. pneumoniae KPC-2 carbapenemase (enzymes involved in infectivity mechanisms), and of ovine COX-2. Overall, our study provides credence on the ethnomedicinal use of the Philippine medicinal plant P. ophthalmicus as traditional plant-based adjuvant to treat bacterial conjunctivitis and other related infections. The antibacterial activities and selective COX-2 inhibition observed for limacusine (2) point to its role as the biologically active constituent of P. ophthalmicus. A limited number of drugs with COX-2 inhibitory properties like celecoxib also confer antibacterial activity. Thus, tetrahydrobisbenzyl alkaloids, especially 2, are promising pharmaceutical inspirations for developing treatments of bacterial/inflammation-related infections.

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“…The genus Uvaria (family Annonaceae) is a prolific source of pharmacologically active natural products. Chemical efforts on different species elaborated secondary metabolites with wide array of biological activities including anti-cancer, anti-inflammatory, antitubercular, antioxidant and antimicrobial activities [14][15][16][17][18][19][20][21]. Despite numerous studies on several species of the genus Uvaria, limited efforts describing the phytochemical constituents and biological activities are reported for the endemic Philippine medicinal plant, Uvaria alba.…”

Section: Introductionmentioning

confidence: 99%

Antiproliferative, cholinesterase and phosphodiesterase inhibitory activity of the DCM sub-extract of Uvaria alba: In vitro and in silico perspectives

Quimque¹,

Notarte

letada³

et al. 2020

Preprint

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<div>Aims: To evaluate the in vitro antiproliferative, anticholinesterase and anti-phosphodiesterase activities of the sub-extracts of Uvaria alba (family Annonaceae) and explore putative binding mechanisms of its chemical constituents in silico. <br></div><div><br></div><div>Main methods: U. alba sub-extracts, obtained by solvent-solvent partition, were subjected to antiproliferative and cytotoxicity screening against chronic myelogenous leukemia (K-562) and human cervical cancer (HeLa) cells, respectively. Inhibitory assays against acetylcholinesterase (AChE) and phosphodiesterase (PDE4 B2) enzymes were also performed. The dichloromethane sub-extract (UaD) was chemically profiled using LC-HR-ESIMS-QToF to identify secondary metabolites 1–18. Molecular docking and molecular dynamics simulations were performed to determine the affinity of the putatively annotated metabolites against PDE4 B2B, AChE, ubiquitin specific peptidase 14 (USP14), and Kelch-like ECH-associated protein 1 (Keap1). In addition, DFT calculations were also performed to demonstrate Michael addition reaction between electrophilic cytotoxic metabolites and Cys151 of the Keap1-BTB domain. <br></div><div><br></div><div>Key findings: UaD showed antiproliferative and cytostatic activities against K-562 and HeLa, respectively, and inhibitory activities against AChE and PDE4 B2. Meanwhile, its polyphenolic constituents 3-(3,4-dihydroxybenzyl)-3’,4’,6-trihydroxy-2,4-dimethoxychalcone (8) and grandifloracin (15) showed favorable binding to AChE and Keap1-BTB domain, respectively. The most electrophilic and kinetically stable grandifloracin (15), favorably formed a beta-addition adduct with the Cys151 of Keap1 via Michael addition. The top-ranked ligand-protein complexes attained dynamic stability at 50-ns simulations with high free energy of binding. The top-ranked compounds also conferred favorable in silico pharmacokinetic properties. <br></div><div><br></div><div>Significance: The study highlights the role of U. alba secondary metabolites as potential inhibitors against the aforementioned target proteins in an effort to discover new drug leads for cancer and Alzheimer’s.</div>

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Antitubercular and cytotoxic polyoxygenated cyclohexane derivatives from Uvaria grandiflora

Cited by 14 publications

References 10 publications

Antioxidant and antimicrobial alkaloids isolated from twigs of Uvaria grandiflora Roxb.

Antioxidant and antimicrobial alkaloids isolated from twigs of Uvaria grandiflora Roxb.

Antibacterial and COX-2 Inhibitory Tetrahydrobisbenzylisoquinoline Alkaloids from the Philippine Medicinal Plant Phaeanthus ophthalmicus

Antiproliferative, cholinesterase and phosphodiesterase inhibitory activity of the DCM sub-extract of Uvaria alba: In vitro and in silico perspectives

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