Structure–activity relationship studies of new rifamycins containing l -amino acid esters as inhibitors of bacterial RNA polymerases

Czerwonka, Dominika; Domagalska, Joanna; Pyta, Krystian; Kubicka, Marcelina; Pecyna, Paulina; Gajęcka, Marzena; Przybylski, Piotr

doi:10.1016/j.ejmech.2016.03.061

Cited by 15 publications

(15 citation statements)

References 27 publications

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“…As the representative members of the ansamycin family, rifamycins were first isolated from Amycolatopsis mediterranei S699 in 1957 [3][4][5]. Semi-synthetic rifamycin derivatives, such as rifampicin, rifapentine and rifambutin, have long been the first-line antituberculosis drugs since the mid-1960s, and are effective in combating leprosy and tuberculosis involved in AIDSrelated mycobacterial infections [6][7][8][9]. However, Mycobacterium tuberculosis has developed significantly increased resistance to rifamycin antibiotics due to their extensive clinical use during recent decades [10,11].…”

Section: Introductionmentioning

confidence: 99%

Rifamycin W Analogues from Amycolatopsis mediterranei S699 Δrif-orf5 Strain

Shi

Song

et al. 2021

Biomolecules

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Rifamycin W, the most predominant intermediate in the biosynthesis of rifamycin, needs to undergo polyketide backbone rearrangement to produce rifamycin B via an oxidative cleavage of the C-12/C-29 double bond. However, the mechanism of this putative oxidative cleavage has not been characterized yet. Rif-Orf5 (a putative cytochrome P450 monooxygenase) was proposed to be involved in the cleavage of this olefinic moiety of rifamycin W. In this study, the mutant strain Amycolatopsis mediterranei S699 Δrif-orf5 was constructed by in-frame deleting the rif-orf5 gene to afford thirteen rifamycin W congeners (1–13) including seven new ones (1–7). Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Presumably, compounds 1–4 were derivatized from rifamycin W via C-5/C-11 retro-Claisen cleavage, and compounds 1–3, 9 and 10 featured a hemiacetal. Compounds 5–7 and 11 showed oxygenations at various sites of the ansa chain. In addition, compounds 1–3 exhibited antibacterial activity against Staphylococcus aureus with minimal inhibitory concentration (MIC) values of 5, 40 and 0.5 µg/mL, respectively. Compounds 1 and 3 showed modest antiproliferative activity against HeLa and Caco-2 cells with half maximal inhibitory concentration (IC50) values of about 50 µM.

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Section: Introductionmentioning

confidence: 99%

Rifamycin W Analogues from Amycolatopsis mediterranei S699 Δrif-orf5 Strain

Shi

Song

et al. 2021

Biomolecules

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“…The downregulation of this pathway suggested that squalene@CPC nanoemulsions had a profound effect on the transcription of DNA to RNA. A similar example is rifamycin binding to the β subunit of RNAP as the antibacterial mechanism of action 44,45. Compared to RNAP, we did not find any significant concordance with the proteins involving oxidative stress, Fenton reaction, and the Krebs cycle.…”

Section: Discussionmentioning

confidence: 60%

<p>The Droplet-Size Effect Of Squalene@cetylpyridinium Chloride Nanoemulsions On Antimicrobial Potency Against Planktonic And Biofilm MRSA</p>

Fang¹,

Lin²,

Wang³

et al. 2019

IJN

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BackgroundIt is important to explore the interaction between antibacterial nanoparticles and microbes for understanding bactericidal activity and developing novel applications. It is possible that the nanoparticulate size can govern the antibacterial potency.PurposeThe purpose of this study was to evaluate the antimicrobial and antibiofilm properties of cetylpyridinium chloride (CPC)–decorated nanoemulsions against methicillin-resistant Staphylococcus aureus (MRSA).MethodsThe droplet size could be adjusted by varying the percentage of squalene, the main ingredient of the oily core.ResultsWe fabricated cationic nanoemulsions of three different sizes, 55, 165, and 245 nm. The nanoemulsions showed greater storage stability than the self-assembled CPC micelles. The tested nanoemulsions exhibited more antimicrobial activity against Gram-positive bacteria than Gram-negative bacteria and fungi. The killing of MRSA was mainly induced by direct cell-membrane damage. This rupture led to the leakage of cytoplasmic DNA and proteins. The nanoemulsions might also degrade the DNA helix and disturb protein synthesis. The proteomic analysis indicated the significant downregulation of DNA-directed RNA polymerase (RNAP) subunits β and β’. The antibacterial effect of nanoemulsions increased with decreasing droplet size in the biofilm MRSA but not planktonic MRSA. The small-sized nanoemulsions had potent antibiofilm activity that showed a colony-forming unit (CFU) reduction of 10-fold compared with the control. The loss of total DNA concentration also negatively correlated with the nanoemulsion size.ConclusionThe present report established a foundation for the development of squalene@CPC nanosystems against drug-resistant S. aureus.

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“…9b). 51,53,[58][59][60] In one of these alternative binding patterns concerning rifampicin, the protonated piperazine arm at a slightly altered conformation takes part in a very strong Hbond interaction (rifampicin)N + -H.OOC-(E445 RNAP ) of the salt-type character (H-bond donor .acceptor $2.6 Å; angle $170 ). 53 It should be mentioned that new models for rifampicin and its amine congeners explained the structure-activity relationships at changing C(3)-substituent of congeners having comparable lipophilicity and water solubility.…”

Section: Structural Aspects Of Naphthalenoid Ansamycins Influencing T...mentioning

confidence: 99%

Modifications, biological origin and antibacterial activity of naphthalenoid ansamycins

Skrzypczak

Przybylski

2022

Nat. Prod. Rep.

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Structure–activity relationship studies of new rifamycins containing l -amino acid esters as inhibitors of bacterial RNA polymerases

Cited by 15 publications

References 27 publications

Rifamycin W Analogues from Amycolatopsis mediterranei S699 Δrif-orf5 Strain

Rifamycin W Analogues from Amycolatopsis mediterranei S699 Δrif-orf5 Strain

<p>The Droplet-Size Effect Of Squalene@cetylpyridinium Chloride Nanoemulsions On Antimicrobial Potency Against Planktonic And Biofilm MRSA</p>

Modifications, biological origin and antibacterial activity of naphthalenoid ansamycins

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