Reaction of Papaverine with Baran DiversinatesTM

Egbewande, Folake A; Coster, Mark J.; Jenkins, Ian D.; Davis, Rohan A.

doi:10.3390/molecules24213938

Cited by 6 publications

(6 citation statements)

References 41 publications

(64 reference statements)

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“…After the FDA’s approval of auranofin (tetra- O -acetylglucose-1-thiolgold(I) triethylphosphine complex) as a therapy for rheumatoid arthritis, the gold-based drugs have attracted special attentioin. The exploitation of gold complexes has led to vast diversity of gold compounds of biological relevance, including anti-cancer, anti-inflammatory and antiparasitic agents [ 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Papaverine Metal Complexes with Potential Anticancer Activities

et al. 2020

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Cancer is one of the leading causes of death worldwide. Although several potential therapeutic agents have been developed to efficiently treat cancer, some side effects can occur simultaneously. Papaverine, a non-narcotic opium alkaloid, is a potential anticancer drug that showed selective antitumor activity in various tumor cells. Recent studies have demonstrated that metal complexes improve the biological activity of the parent bioactive ligands. Based on those facts, herein we describe the synthesis of novel papaverine–vanadium(III), ruthenium(III) and gold(III) metal complexes aiming at enhancing the biological activity of papaverine drug. The structures of the synthesized complexes were characterized by various spectroscopic methods (IR, UV–Vis, NMR, TGA, XRD, SEM). The anticancer activity of synthesized metal complexes was evaluated in vitro against two types of cancer cell lines: human breast cancer MCF-7 cells and hepatocellular carcinoma HepG-2 cells. The results revealed that papaverine-Au(III) complex, among the synthesized complexes, possess potential antimicrobial and anticancer activities. Interestingly, the anticancer activity of papaverine–Au(III) complex against the examined cancer cell lines was higher than that of the papaverine alone, which indicates that Au-metal complexation improved the anticancer activity of the parent drug. Additionally, the Au complex showed anticancer activity against the breast cancer MCF-7 cells better than that of cisplatin. The biocompatibility experiments showed that Au complex is less toxic than the papaverine drug alone with IC50 ≈ 111 µg/mL. These results indicate that papaverine–Au(III) complex is a promising anticancer complex-drug which would make it a suitable candidate for further in vivo investigations.

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Section: Introductionmentioning

confidence: 99%

Novel Papaverine Metal Complexes with Potential Anticancer Activities

et al. 2020

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“…To further expand our library and thus explore SARs within the halogenated series, we sought to engage Baran’s innovative Diversinate™ chemistry for the late-stage trifluoromethylation of N -Boc protected thiaplakortone A [ 26 , 27 ]. Consequently, a mixture of compound 2 and zinc trifluoromethanesulfinate in CH 2 Cl 2 /H 2 O was stirred for 1 h at 4 °C (see Scheme 2 ).…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Antimalarial Evaluation of Halogenated Analogues of Thiaplakortone A

et al. 2023

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The incorporation of bromine, iodine or fluorine into the tricyclic core structure of thiaplakortone A (1), a potent antimalarial marine natural product, is reported. Although yields were low, it was possible to synthesise a small nine-membered library using the previously synthesised Boc-protected thiaplakortone A (2) as a scaffold for late-stage functionalisation. The new thiaplakortone A analogues (3–11) were generated using N-bromosuccinimide, N-iodosuccinimide or a Diversinate™ reagent. The chemical structures of all new analogues were fully characterised by 1D/2D NMR, UV, IR and MS data analyses. All compounds were evaluated for their antimalarial activity against Plasmodium falciparum 3D7 (drug-sensitive) and Dd2 (drug-resistant) strains. Incorporation of halogens at positions 2 and 7 of the thiaplakortone A scaffold was shown to reduce antimalarial activity compared to the natural product. Of the new compounds, the mono-brominated analogue (compound 5) displayed the best antimalarial activity with IC50 values of 0.559 and 0.058 μM against P. falciparum 3D7 and Dd2, respectively, with minimal toxicity against a human cell line (HEK293) observed at 80 μM. Of note, the majority of the halogenated compounds showed greater efficacy against the P. falciparum drug-resistant strain.

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“…In addition, the fungal aromatic peroxygenase (AaP) was reported to catalyze the N-oxygenation of pyridine and related compounds (Ullrich et al, 2008). Nitrogen-rich heterocyclic compounds are used to treat various human diseases, and these motifs are found in many isoquinoline alkaloid drugs (Egbewande et al, 2019) IUCrJ (2021). 8, 684-694 Figure 2 HPLC chromatogram and LC-MS spectra (inside the box) for (a) papaverine and (b) tetrahydropalmatine.…”

Section: Functional Characterization Of Cyp105d18mentioning

confidence: 99%

“…However, modified papaverine may have better efficacy and reduced cytotoxicity and can easily be metabolized by the body. Chemical modification of papaverine for C-H functionalization, N-oxidation (Egbewande et al, 2019) and Odemethylation has been reported (Brossi & Teitel, 1970). These classical approaches are time-consuming and costly and may suffer from poor regio-selectivity compared with enzymecatalyzed reactions.…”

Section: Introductionmentioning

confidence: 99%

Characterization of high-H₂O₂-tolerant bacterial cytochrome P450 CYP105D18: insights into papaverine N-oxidation

Pardhe

Jeong

et al. 2021

Int Union Crystallogr J

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The bacterial CYP105 family is involved in secondary metabolite biosynthetic pathways and plays essential roles in the biotransformation of xenobiotics. This study investigates the newly identified H2O2-mediated CYP105D18 from Streptomyces laurentii as the first bacterial CYP for N-oxidation. The catalytic efficiency of CYP105D18 for papaverine N-oxidation was 1.43 s−1 µM −1. The heme oxidation rate (k) was low (<0.3 min−1) in the presence of 200 mM H2O2. This high H2O2 tolerance capacity of CYP105D18 led to higher turnover prior to heme oxidation. Additionally, the high-resolution papaverine complexed structure and substrate-free structure of CYP105D18 were determined. Structural analysis and activity assay results revealed that CYP105D18 had a strong substrate preference for papaverine because of its bendable structure. These findings establish a basis for biotechnological applications of CYP105D18 in the pharmaceutical and medicinal industries.

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Reaction of Papaverine with Baran DiversinatesTM

Cited by 6 publications

References 41 publications

Novel Papaverine Metal Complexes with Potential Anticancer Activities

Novel Papaverine Metal Complexes with Potential Anticancer Activities

Synthesis and Antimalarial Evaluation of Halogenated Analogues of Thiaplakortone A

Characterization of high-H₂O₂-tolerant bacterial cytochrome P450 CYP105D18: insights into papaverine N-oxidation

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Reaction of Papaverine with Baran DiversinatesTM

Cited by 6 publications

References 41 publications

Novel Papaverine Metal Complexes with Potential Anticancer Activities

Novel Papaverine Metal Complexes with Potential Anticancer Activities

Synthesis and Antimalarial Evaluation of Halogenated Analogues of Thiaplakortone A

Characterization of high-H2O2-tolerant bacterial cytochrome P450 CYP105D18: insights into papaverine N-oxidation

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Characterization of high-H₂O₂-tolerant bacterial cytochrome P450 CYP105D18: insights into papaverine N-oxidation