Synthetic berberine derivatives as potential new drugs

Filli, Mensura Sied; Ibrahim, Ahmed Abdalla; Kesse, Samuel; Aquib, Md; Boakye‐Yiadom, Kofi Oti; Farooq, Muhammad Asim; Raza, Faisal; Zhang, Yubin; Wang, Bo

doi:10.1590/s2175-97902020000318835

Cited by 5 publications

(3 citation statements)

References 69 publications

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“…However, the therapeutic utility of berberine is compromised due to its undesirable pharmacokinetic properties and its poor water solubility. This limitation could, however, be overcome by appropriate structural modifications on its scaffold, leading to the synthesis of various berberine derivatives with improved pharmacological and pharmacokinetic profiles [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli

Somma

Canè

Rotondo

et al. 2023

IJMS

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Medicinal plants belonging to the genus Berberis may be considered an interesting source of drugs to counteract the problem of antimicrobial multiresistance. The important properties associated with this genus are mainly due to the presence of berberine, an alkaloid with a benzyltetrahydroisoquinoline structure. Berberine is active against both Gram-negative and Gram-positive bacteria, influencing DNA duplication, RNA transcription, protein synthesis, and the integrity of the cell surface structure. Countless studies have shown the enhancement of these beneficial effects following the synthesis of different berberine analogues. Recently, a possible interaction between berberine derivatives and the FtsZ protein was predicted through molecular docking simulations. FtsZ is a highly conserved protein essential for the first step of cell division in bacteria. The importance of FtsZ for the growth of numerous bacterial species and its high conservation make it a perfect candidate for the development of broad-spectrum inhibitors. In this work, we investigate the inhibition mechanisms of the recombinant FtsZ of Escherichia coli by different N-arylmethyl benzodioxolethylamines as berberine simplified analogues appropriately designed to evaluate the effect of structural changes on the interaction with the enzyme. All the compounds determine the inhibition of FtsZ GTPase activity by different mechanisms. The tertiary amine 1c proved to be the best competitive inhibitor, as it causes a remarkable increase in FtsZ Km (at 40 μM) and a drastic reduction in its assembly capabilities. Moreover, a fluorescence spectroscopic analysis carried out on 1c demonstrated its strong interaction with FtsZ (Kd = 26.6 nM). The in vitro results were in agreement with docking simulation studies.

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Section: Discussionmentioning

confidence: 99%

A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli

Somma

Canè

Rotondo

et al. 2023

IJMS

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“…Plants containing berberine and palmatine have been exploited for centuries in traditional oriental medicine as a remedy for various ailments and diseases. Therapeutic effects of berberine include lowering body temperature, detoxification, analgesic, spasmolytic, and antihypertensive activity ( Filli et al, 2020 ). Palmatine has been reported to be used as a remedy in jaundice- and liver-related diseases, hypertension, inflammation, dysentery, as well as in infections of the urinary, gastrointestinal and respiratory tracts ( Tarabasz and Kukula-Koch, 2020 ).…”

Section: Plant Extracts And/or Active Constituents With Anticonvulsan...mentioning

confidence: 99%

Zebrafish as a robust preclinical platform for screening plant-derived drugs with anticonvulsant properties—a review

Knap,

Nieoczym,

Kundap

et al. 2023

Front. Mol. Neurosci.

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Traditionally, selected plant sources have been explored for medicines to treat convulsions. This continues today, especially in countries with low-income rates and poor medical systems. However, in the low-income countries, plant extracts and isolated drugs are in high demand due to their good safety profiles. Preclinical studies on animal models of seizures/epilepsy have revealed the anticonvulsant and/or antiepileptogenic properties of, at least some, herb preparations or plant metabolites. Still, there is a significant number of plants known in traditional medicine that exert anticonvulsant activity but have not been evaluated on animal models. Zebrafish is recognized as a suitable in vivo model of epilepsy research and is increasingly used as a screening platform. In this review, the results of selected preclinical studies are summarized to provide credible information for the future development of effective screening methods for plant-derived antiseizure/antiepileptic therapeutics using zebrafish models. We compared zebrafish vs. rodent data to show the translational value of the former in epilepsy research. We also surveyed caveats in methodology. Finally, we proposed a pipeline for screening new anticonvulsant plant-derived drugs in zebrafish (“from tank to bedside and back again”).

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“…Thus, gut microbiota (Wang et al, 2015;Ai et al, 2021) may provide a good strategy to overcome the poor oral pharmacokinetics of this class of alkaloids for their use as bloodstage antiplasmodial agent. Some studies have reported synthetic derivatives of berberine with optimum therapeutic effect against different diseases (Filli et al, 2022). Thus, in one such study (Bahar et al, 2011), a semi-synthetic berberine analogue 5,6-didehydro-8,8-diethyl-13oxodihydroberberine chloride has shown greatly enhanced antiplasmodial activity (IC50 36 nM) in comparison to berberine (IC50 0.85 µM).…”

Section: Introductionmentioning

confidence: 99%

Antiplasmodial activity, in silico ADME and mammalian cell cytotoxicity of a synthetic protoberberine alkaloid, coralyne

Erhunse,

Dinkar

2024

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Coralyne is a synthetic protoberberine alkaloid with anticancer activity and selectivity superior to that of berberine, its congener. As berberine is gifted with antiplasmodial activity, this study assessed the antiplasmodial activity of coralyne against erythrocytic stages of the malaria parasite in culture. Parasites were cultured by adopting the method described by Trager and Jensen in 1976. Following this, parasites were exposed at ring stage to increasing doses of coralyne to enable us compute the IC50. Further, given that berberine is a substrate of the efflux transporter permeability glycoprotein (P-gp), in silico techniques were used to study the pharmacokinetics of oral coralyne. Coralyne showed excellent potency (IC50Pf3D7: 0.52 µg/ml) against chloroquine sensitive strain and a little less potency (IC50PfINDO: 1.15 µg/ml) against the chloroquine resistant malaria parasite strain (Resistance index: 2.21). Further, with CC50HEK: >100 µg/ml, it was non-toxic to mammalian cells. However, in silico absorption, distribution, metabolism and excretion (ADME) studies predicts that like berberine, coralyne may also have poor oral bioavailability thus limiting its usefulness as an orally deliverable antimalarial agent. Given the negative impact of low bioavailability in the development of protoberberine alkaloids as antimalarials, synthesizing analogues of coralyne with nanomolar potency against the malaria parasite and improved oral pharmacokinetics may be a good strategy for the future.

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Synthetic berberine derivatives as potential new drugs

Cited by 5 publications

References 69 publications

A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli

A Comparative Study of the Inhibitory Action of Berberine Derivatives on the Recombinant Protein FtsZ of E. coli

Zebrafish as a robust preclinical platform for screening plant-derived drugs with anticonvulsant properties—a review

Antiplasmodial activity, in silico ADME and mammalian cell cytotoxicity of a synthetic protoberberine alkaloid, coralyne

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