Synthetic access to thiolane-based therapeutics and biological activity studies

Rodrigues, Lima; Tilve, Santosh G.; Majik, Mahesh S.

doi:10.1016/j.ejmech.2021.113659

Cited by 10 publications

(6 citation statements)

References 91 publications

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“…Searching for novel drugs sometimes leads back to compounds known for decades. An example of this occurred with albomycins, discovered in the 1940s and produced by Streptomyces griseus (Rodrigues et al 2021 ). Three of these natural compounds have been synthesized (δ 1 (1a), δ 2 (1b), and ε (1c)), and their effect against infections by microorganisms such as Streptococcus pneumoniae and Staphylococcus aureus leads to the promise of candidates for treatments (Al Shaer et al 2020 ).…”

Section: Siderophores Used As Antimicrobial Agentsmentioning

confidence: 99%

Opportunities and challenges of microbial siderophores in the medical field

Passari,

Ruiz-Villafán,

Cruz-Bautista

et al. 2023

Appl Microbiol Biotechnol

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Siderophores are low-molecular-weight secondary metabolites that function as iron chelators. Under iron-deficiency conditions, they are produced by a wide variety of microbes, allowing them to increase their iron uptake. The primary function of these compounds is the environmental iron scavenging and its transport into the cytosol. Iron is then reduced to its ferrous form to operate as an enzymatic cofactor for various functions, including respiration, nitrogen fixation, photosynthesis, methanogenesis, and amino acid synthesis. Depending on their functional group, siderophores are classified into hydroxamate, catecholate, phenolate, carboxylate, and mixed types. They have achieved great importance in recent years due to their medical applications as antimicrobial, antimalarial, or anticancer drugs, vaccines, and drug-delivery agents. This review integrates current advances in specific healthcare applications of microbial siderophores, delineating new opportunities and challenges as viable therapies to fight against diseases that represent crucial public health problems in the medical field.Key points• Siderophores are low-molecular-weight secondary metabolites functioning as iron chelators.• The siderophore’s properties offer viable options to face diverse clinical problems.• Siderophores are alternatives for the enhancement of antibiotic activities.

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Section: Siderophores Used As Antimicrobial Agentsmentioning

confidence: 99%

Opportunities and challenges of microbial siderophores in the medical field

Passari,

Ruiz-Villafán,

Cruz-Bautista

et al. 2023

Appl Microbiol Biotechnol

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“…The 1 H NMR spectroscopic data were consistent with those reported in the literature. 27e In conclusion, the unprecedented DAST-mediated deoxygenative fluorination of benzoyl (24), TBDPS (25), and Bn (26, 29) protected 1-(-D-4-thioarabinofuranosyl)uracil at the sugar moiety was examined. Three kinds of products, the target thiolane Ns (30, 32, 34, 36), the ring-contracted thietane Ns (31, 33, 35, 37), and anhydro Ns (21,22,23) compounds were formed.…”

Section: Paper Synthesismentioning

confidence: 99%

“…Among their sugarmodified analogues, 4′-thionucleosides, in which the oxygen atom in the furanose ring is replaced with a sulfur atom, have attracted much attention since the discovery of the antiviral and antitumor activities of 4′-thiothymidine (1) and 2′-deoxy-4′-thiocytidine (2) (Figure 1). [22][23][24][25][26] The synthesis of 2′-substituted derivatives 3-6 of 2 and their evaluation for antineoplastic activity have been reported (Figure 2). 27 In the study, 4′-thioFAC 4 has emerged as a highly potent antineoplastic agent.…”

mentioning

confidence: 99%

DAST-Mediated Fluorination of 1-[4-Thio-β-d-arabinofuranosyl]uracil: Investigation of Thiolane vs Thietane Formation and Stereoselective Synthesis of 4′-ThioFAC

Haraguchi¹,

Hannda²,

Wakasugi³

et al. 2022

Synthesis

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The unprecedented DAST-mediated (DAST = diethylaminosulfur trifluoride) deoxygenative fluorination of benzoyl-, TBDPS-, and Bn-protected 1-(β-d-4-thioarabinofuranosyl)uracil at the sugar portion was examined. Three kinds of nucleoside (Ns) products were formed: target thiolane Ns, ring-contracted thietane Ns, and anhydro Ns products. The reaction pathway was determined by the electronic effect of the protecting groups at the sugar and base moieties. The benzoylated uracil starting material gave the 2,2′-anhydronucleoside (anhydro Ns) as a major product, whereas the silylated and benzylated starting materials furnished the corresponding fluorinated products, in which the ring-contracted thietanes predominantly formed. The desired thiolane Ns could be obtained as major product by the addition of a pyridine derivative as an additive. Upon reacting N 3-benzoylated 1-(β-d-4-thioarabinofuranosyl)uracil with DAST in the presence of 2,4,6-collidine, the target 2′-deoxy-2′-β-fluoro-4′-thiouracil nucleoside could be obtained in 72% isolated yield along with the corresponding thietane Ns (7%) and anhydro Ns (3%) (thiolane Ns/thietane Ns/anhydro Ns = 10.3:1.00:0.43), with recovery of the starting material (12%). In this study, the first stereoselective synthesis of the β-anomer of 1-(2-deoxy-2-fluoro-4-thio-β-d-arabino-pentofuranosyl)cytosine (4′-thioFAC) has been developed.

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“…Figure 1 Structure of anti-HBV nucleoside/nucleotide derivatives 4′-Thionucleosides, in which the oxygen atom in the furanose ring is replaced by a sulfur atom, have attracted much attention since the discovery of the antiviral and antitumor activities of 4′-thiothymidine (1) and 2′-deoxy-4′thiocytidine (2) (Figure 2). [2][3][4][5][6] The 4′-thionucleoside 2′-de-…”

mentioning

confidence: 99%

Regio- and Stereoselective Synthesis of 2′-Deoxy-4′-thioguanine Nucleosides: Evaluation of Anti-Hepatitis B Virus Activity and Cytotoxicity Leading to Improved Selectivity Index by 4′-C-Cyanation

Haraguchi,

Kumamoto,

Imoto

et al. 2023

Synlett

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An N 9-regio- and β-anomer-selective 4′-thioglycosidation of purine bases has been developed. The reaction between a 2-deoxy-2-iodo-4-thioribofuranosyl glycosyl donor and N-(6-chloro-9H-purin-2-yl)-2-methylpropanamide gave the corresponding 2′-deoxy-4′-thiopurine nucleoside in 87% yield along with its N 7-regioisomer in 6% yield, without the formation of the α-anomer. By using a derivative obtained from 17, a practical chemical synthesis of 2′-deoxy-4′-thioguanosine was developed. 4′-α-C-Cyano-2′-deoxy-4′-thioguanosine was synthesized, starting from a 4-(acetoxymethyl)-2-deoxy-2-iodo-4-thioribofuranose derivative as a glycosyl donor. An evaluation of the anti-hepatitis B virus (HBV) activity and the cytotoxicity toward the host cell revealed that 4'-C-cyano-2'-deoxy-4'-thioguanosine exhibited about 100 times more potent anti-HBV activity than 2′-deoxy-4′-thioguanosine with a comparative cytotoxicity, resulting in the identification of a novel molecule having better selectivity index value than that of 2′-deoxy-4′-thioguanosine. This finding might provide a guideline for the development of the next generation of anti-HBV agents.

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Synthetic access to thiolane-based therapeutics and biological activity studies

Cited by 10 publications

References 91 publications

Opportunities and challenges of microbial siderophores in the medical field

Opportunities and challenges of microbial siderophores in the medical field

DAST-Mediated Fluorination of 1-[4-Thio-β-d-arabinofuranosyl]uracil: Investigation of Thiolane vs Thietane Formation and Stereoselective Synthesis of 4′-ThioFAC

Regio- and Stereoselective Synthesis of 2′-Deoxy-4′-thioguanine Nucleosides: Evaluation of Anti-Hepatitis B Virus Activity and Cytotoxicity Leading to Improved Selectivity Index by 4′-C-Cyanation

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Synthetic access to thiolane-based therapeutics and biological activity studies

Cited by 10 publications

References 91 publications

Opportunities and challenges of microbial siderophores in the medical field

Opportunities and challenges of microbial siderophores in the medical field

DAST-Mediated Fluorination of 1-[4-Thio-β-d-arabinofuranosyl]uracil: Investigation of Thiolane vs Thietane Formation and Stereoselective Synthesis of 4′-ThioFAC

Regio- and Stereoselective Synthesis of 2′-Deoxy-4′-thioguanine Nucleosides: Evaluation of Anti-Hepatitis B Virus Activity and ­Cytotoxicity Leading to Improved Selectivity Index by 4′-C-Cyanation

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Regio- and Stereoselective Synthesis of 2′-Deoxy-4′-thioguanine Nucleosides: Evaluation of Anti-Hepatitis B Virus Activity and Cytotoxicity Leading to Improved Selectivity Index by 4′-C-Cyanation