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1.
Carbohydr Res ; 535: 108992, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38091695

ABSTRACT

2,6-Dideoxy sugars constitute an important class of anticancer antibiotics natural products and serve as essential medicinal tools for carbohydrate-based drug discovery and vaccine development. In particular, 2-deoxy ʟ-fucose or ʟ-oliose is a rare sugar and vital structural motif of several potent antifungal and immunosuppressive bioactive molecules. Herein, we devised a reagent-controlled stereo and chemoselective activation of ʟ-fucal, enabling the distinctive glycosylation pathways to access the rare ʟ-oliose and 2,3-unsaturated ʟ-fucoside. The milder oxo-philic Bi(OTf)3 catalyst induced the direct 1,2-addition predominantly, whereas B(C6F5)3 promoted the allylic Ferrier-rearrangement of the enol-ether moiety in ʟ-fucal glycal donor, distinguishing the competitive mechanisms. The reagent-tunable modular approach is highly advantageous, employing greener catalysts and atom-economical transformations, expensive ligand/additive-free, and probed for a diverse range of substrates comprising monosaccharides, amino-acids, bioactive natural products, and drug scaffolds embedded with susceptible or labile functionalities.


Subject(s)
Biological Products , Monosaccharides , Indicators and Reagents , Glycosylation , Monosaccharides/chemistry , Fucose , Catalysis , Stereoisomerism
2.
Carbohydr Res ; 523: 108705, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36370626

ABSTRACT

We herein report a convenient and highly stereocontrolled approach for rare and vital ᴅ-talo and ᴅ-gulo sugars directly from economical ᴅ-galactal through dual ruthenium-catalysis. The stereo-divergent strategy involves Ru(III)Cl3-catalyzed Ferrier glycosylation of ᴅ-galactal to give 2,3-unsaturated ᴅ-galactopyranoside, further selective functionalization of C-4 and C-6 position with diverse protecting groups and dihydroxylation with Ru(VIII)O4 generated in situ providing access to talo/gulo isomers. The α-anomeric stereoselectivity and syn-diastereoselectivity in glycosylation-dihydroxylation steps have been predominantly achieved by judicious selection of stereoelectronically diverse protecting groups. The synthetic utility of the dual-ruthenium catalysis was demonstrated for efficiently assembling the ᴅ-talose and/or ᴅ-gulose sugars in natural products and bioactive scaffolds.


Subject(s)
Ruthenium , Sugars , Stereoisomerism , Catalysis
3.
Org Lett ; 24(2): 575-580, 2022 01 21.
Article in English | MEDLINE | ID: mdl-34995079

ABSTRACT

Bi(OTf)3 promoted direct and highly stereoselective glycosylation of "disarmed" and "armed" glycals to synthesize 2-deoxyglycosides has been reported. The tunable and solvent-controlled chemoselective activation of deactivated glycal donors distinguishing the competitive Ferrier and 1,2-addition pathways was discovered to improve substrate scope. The practical versatility of the method has been amply demonstrated with the oligosaccharide syntheses and 2-deoxyglycosylation of high-value natural products and drugs.

4.
ACS Omega ; 6(40): 26623-26639, 2021 Oct 12.
Article in English | MEDLINE | ID: mdl-34661016

ABSTRACT

The photolytic radical-induced vicinal azidooxygenation of synthetically important and diverse functionalized substrates including unactivated alkenes is reported. The photoredox-catalyst/additive-free protocol enables intermolecular oxyazidation by simultaneously incorporating two new functionalities; C-O and C-N across the C=C double bond in a selective manner. Mechanistic investigations reveal the intermediacy of the azidyl radical facilitated via the photolysis of λ3-azidoiodane species and cascade proceeding to generate an active carbon-centered radical. The late-stage transformations of azido- and oxy-moieties were amply highlighted by assembling high-value drug analogs and bioactive skeletons.

5.
RSC Adv ; 11(31): 19310-19315, 2021 May 24.
Article in English | MEDLINE | ID: mdl-35478635

ABSTRACT

A Me3SI-mediated simple and efficient protocol for the chemoselective deprotection of acetyl groups has been developed via employing KMnO4 as an additive. This chemoselective deacetylation is amenable to a wide range of substrates, tolerating diverse and sensitive functional groups in carbohydrates, amino acids, natural products, heterocycles, and general scaffolds. The protocol is attractive because it uses an environmentally benign reagent system to perform quantitative and clean transformations under ambient conditions.

6.
Org Biomol Chem ; 18(25): 4848-4862, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32608448

ABSTRACT

Selective activation of "armed' and ''disarmed" glycal donors enabling the stereo-controlled glycosylations by employing Cu(ii)-catalyst as the promoter has been realized. The distinctive stereochemical outcome in the process is mainly influenced by the presence of diverse protecting groups on the donor and the solvent system employed. The protocol is compatible with a variety of aglycones including carbohydrates, amino acids, and natural products to access deoxy-glycosides and glycoconjugates with high α-anomeric selectivity. Notably, the synthetic practicality of the method is amply verified for the stereoselective assembling of trisaccharides comprising 2-deoxy components. Mechanistic studies involving deuterated experiments validate the syn-diastereoselective 1,2-addition of acceptors on the double bond of armed donors.

7.
Org Lett ; 21(24): 9990-9994, 2019 Dec 20.
Article in English | MEDLINE | ID: mdl-31755275

ABSTRACT

Photoswitchable strategy for selective azidation of structurally diverse olefins under transition-metal-free conditions is reported. The unprecedented reactivity of trimethylsulfonium [bis(azido)iodate(I)] species under visible light allows radical azidooxygenation of the C═C π bond with distinctive selectivity. In the absence of visible light, the reaction proceeds through an ionic intermediate which led to complementary regioselectivity to provide α-alkyl azides. Mechanistic studies reveal that light-controlled regiodivergent azidation involving radical or an ionic pathway can be accomplished with exclusive regioselectivity.

8.
Chem Commun (Camb) ; 55(19): 2833-2836, 2019 Feb 28.
Article in English | MEDLINE | ID: mdl-30766978

ABSTRACT

A visible light-induced vicinal diazidation of various alkenes using stable sulfonium bis(acetoxy)iodate(i) and sodium azide as a radical precursor is described. The trimethylsulfonium [bis(azido)iodate(i)] species, intrinsically generated in situ, demonstrated unprecedented reactivity toward C[double bond, length as m-dash]C π bond-promoting selective azidation under photochemical conditions without any photoredox or metal catalyst. The visible-light stimulated diazidation reaction provides a convenient and straightforward approach to highly prevalent vicinal nitrogen scaffolds of myriad therapeutic importance.

9.
Antiviral Res ; 160: 126-136, 2018 12.
Article in English | MEDLINE | ID: mdl-30393013

ABSTRACT

A small molecule chemical inhibitor CGP57380 that blocks activation of MAPK interacting kinase 1 (MNK1) was found to significantly suppress buffalopox virus (BPXV) replication. BPXV infection was shown to induce MNK1 activation. Depletion of MNK1 by small interfering RNA (siRNA), blocking activation of extracellular regulated kinase (ERK, an upstream activator of MNK1) and disruption of eIF4E/eIF4G interaction (downstream substrate of MNK1 which plays a central role in cap-dependent translation initiation), resulted in reduced BPXV replication, suggesting that ERK/MNK1/eIF4E signaling is a prerequisite for BPXV replication. With the help of time-of-addition and virus step-specific assays, CGP57380 treatment was shown to decrease synthesis of viral genome (DNA). Disruption of ERK/MNK1/eIF4E signaling resulted in reduced synthesis of viral proteins, suggesting that BPXV utilizes cap-dependent mechanism of translation initiation. Therefore, we concluded that decreased synthesis of viral genome in presence of MNK1 inhibitor is the result of reduced synthesis of viral proteins. Furthermore, BPXV was sequentially passaged (P = 40) in presence of CGP57380 or vehicle control (DMSO). As compared to P0 and P40-control viruses, P40-CGP57380 virus replicated at significantly higher (∼10-fold) titers in presence of CGP57380, although a complete resistance could not be achieved. In a BPXV egg infection model, CGP57380 was found to prevent development of pock lesions on chorioallantoic membrane (CAM) as well as associated mortality of the embryonated chicken eggs. We for the first time demonstrated in vitro and in ovo antiviral efficacy of CGP57380 against BPXV and identified that ERK/MNK1 signaling is a prerequisite for synthesis of viral proteins. Our study also describes a rare report about generation of drug-resistant viral variants against a host-targeting antiviral agent.


Subject(s)
Aniline Compounds/pharmacology , Antiviral Agents/pharmacology , DNA, Viral/biosynthesis , Protease Inhibitors/pharmacology , Purines/pharmacology , Vaccinia virus/drug effects , Viral Proteins/biosynthesis , Virus Replication/drug effects , Animals , Chick Embryo , Chickens , Chorioallantoic Membrane/pathology , Drug Resistance, Viral , Ovum/virology , Serial Passage , Vaccinia virus/physiology , Viral Load
10.
Virus Res ; 253: 48-61, 2018 07 15.
Article in English | MEDLINE | ID: mdl-29864503

ABSTRACT

Viruses are obligate intracellular parasites; they heavily depend on the host cell machinery to effectively replicate and produce new progeny virus particles. Following viral infection, diverse cell signaling pathways are initiated by the cells, with the major goal of establishing an antiviral state. However, viruses have been shown to exploit cellular signaling pathways for their own effective replication. Genome-wide siRNA screens have also identified numerous host factors that either support (proviral) or inhibit (antiviral) virus replication. Some of the host factors might be dispensable for the host but may be critical for virus replication; therefore such cellular factors may serve as targets for development of antiviral therapeutics. Mitogen activated protein kinase (MAPK) is a major cell signaling pathway that is known to be activated by diverse group of viruses. MAPK interacting kinase 1 (MNK1) has been shown to regulate both cap-dependent and internal ribosomal entry sites (IRES)-mediated mRNA translation. In this review we have discuss the role of MAPK in virus replication, particularly the role of MNK1 in replication and translation of viral genome.


Subject(s)
Host-Pathogen Interactions , Protein Serine-Threonine Kinases/metabolism , Virus Diseases/enzymology , Virus Replication , Animals , Humans , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Virus Diseases/genetics , Virus Diseases/virology , Viruses/genetics
11.
Infect Ecol Epidemiol ; 8(1): 1450590, 2018.
Article in English | MEDLINE | ID: mdl-29755700

ABSTRACT

Aims: Multiple antimicrobial resistance in Escherichia coli of wild vertebrates is a global concern with scarce assessments on the subject from developing countries that have high human-wild species interactions. We studied the ecology of E. coli in a wintering population of Egyptian Vultures in India to understand temporal changes in both E. coli strains and patterns of antimicrobial resistance. Methods and Results: We ribotyped E. coli strains and assessed antimicrobial resistance from wintering vultures at a highly synanthropic carcass dump in north-west India. Both E. coli occurence (90.32%) and resistance to multiple antimicrobials (71.43%) were very high. Clear temporal patterns were apparent. Diversity of strains changed and homogenized at the end of the Vultures' wintering period, while the resistance pattern showed significantly difference inter-annually, as well as between arrival and departing individuals within a wintering cycle. Significance of study: The carcass dump environment altered both E. coli strains and multiple antimicrobial resistance in migratory Egyptian Vultures within a season. Long-distance migratory species could therefore disseminate resistant E. coli strains across broad geographical scales rendering regional mitigation strategies to control multiple antimicrobial resistance in bacteria ineffective.

12.
Org Biomol Chem ; 16(9): 1508-1518, 2018 02 28.
Article in English | MEDLINE | ID: mdl-29419840

ABSTRACT

An efficient and highly chemoselective iodination of alkynes using a sulfonium iodate(i) electrophilc reagent under metal-free conditions has been realized. The reactivity of sulfonium iodate(i) salt could be significantly diverse in the presence of water as the solvent, enabling the (E)-1,2-diiodoalkenes stereospecifically. This stereodivergent approach is amenable to a wide range of alkyne substrates and demonstrates a diverse functional group tolerance resulting in synthetically valuable 1-iodoalkyne and (E)-vicinal-diiodoalkenes in good to excellent yields (up to 99%) with 100% selectivity under ambient conditions.

13.
Vet Anim Sci ; 6: 1-5, 2018 Dec.
Article in English | MEDLINE | ID: mdl-32734046

ABSTRACT

RFLP analysis of the flagellin (flaA) gene was compared using three different restriction endonucleases i.e DdeI, HinfI and DpnII to determine the genetic diversity among 43 Campylobacter jejuni isolates of poultry origin from the same geographical area. flaA gene was amplified in all the isolates and RFLP analysis showed variations. Dde-based RFLP was found most efficient in discriminating C. jejuni isolates by generating 15 different Dde-RFLP patterns with discriminatory index (D.I) of 0.9258 whereas DpnII produced seven Dpn-RFLP patterns (D.I .= 0.8427). While HinfI enzyme produced only six Hinf-RFLP patterns (D.I .= 0.6977). The discrimination of Dpn-RFLP was comparable to discrimination given by Dde-RFLP analysis, which is generally used to study flaA gene RFLP.

14.
Vet World ; 10(8): 990-998, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28919695

ABSTRACT

Immune challenges are inevitable for livestock that are exposed to a varied range of adverse conditions ranging from environmental to pathogenic stresses. The ß-defensins are antimicrobial peptides, belonging to "defensin" family and therefore acts as the first line of defense against the major infections occurring in dairy cattle including intramammary infections. The better resistance to mastitis displayed by Bos indicus is implicit in the fact that they have better adapted and also has more sequence variation with rare allele conserved due to lesser artificial selection pressure than that of Bos taurus. Among the 58 in silico predicted ß-defensins, only a few have been studied in the aspect of intramammary infections. The data on polymorphisms occurring in various ß-defensin genes is limited in B. indicus, indicating toward higher possibilities for exploring marker for mastitis resistance. The following review shall focus on concisely summarizing the up-to-date research on ß-defensins in B. taurus and discuss the possible scope for research in B. indicus.

15.
Org Biomol Chem ; 14(31): 7529-43, 2016 Aug 21.
Article in English | MEDLINE | ID: mdl-27430994

ABSTRACT

Metal-free, molecular iodine-free direct 1,2-difunctionalization of unactivated alkenes has been reported. The sulfonium iodate(i) reagent efficiently promoted the intermolecular vicinal iodo-functionalization of a diverse range of olefins in a stereo and regioselective manner. This method enables the divergent and straightforward preparation of synthetically useful functionalities; ß-iodocarboxylates, ß-iodohydrins, and ß-iodoethers in a one-step process. Further interconversion of iodo-functionalized derivatives allows easy access to valuable synthetic intermediates en route to biologically active molecules.

16.
Springerplus ; 5: 25, 2016.
Article in English | MEDLINE | ID: mdl-26783509

ABSTRACT

The helicases are motor proteins participating in a range of nucleic acid metabolisms. RNA helicase families are characterized by the presence of conserved motifs. This article reports a comprehensive in silico analysis of Bos taurus DExH/D helicase members. Bovine helicases were identified using the helicase domain sequences including 38 DDX (DEAD box) and 16 DHX (DEAH box) members. Signature motifs were used for the validation of these proteins. Putative sub cellular localization and phylogenetic relationship for these RNA helicases were established. Comparative analysis of these proteins with human DDX and DHX members was carried out. These bovine helicase have been assigned putative physiological functions. Present study of cattle DExH/D helicase will provides an invaluable source for the detailed biochemical and physiological research on these members.

17.
J Org Chem ; 80(14): 7108-16, 2015 Jul 17.
Article in English | MEDLINE | ID: mdl-26098592

ABSTRACT

An efficient and divergent approach to C(2)-C(3) unsaturated glycosyl and α-D-mannopyranosyl sulfones has been developed via ruthenium-promoted direct glycosylation, oxidation, and dihydroxylation from glycal in one-pot. The presence of stoichiometric amounts of NaIO4 and in situ generation of RuO4 from a RuCl3-NaIO4 reagent system were crucial for chemoselective oxidation of sulfide in the presence of an olefin moiety. The dual-role of ruthenium in sequential glycosylation-oxidation-dihydroxylation is amenable to a wide range of thio acceptors to access α-D-mannopyranosyl sulfones in good yields with high regioselectivity.


Subject(s)
Mannose/chemical synthesis , Thiosugars/chemical synthesis , Catalysis , Glycosylation , Mannose/analogs & derivatives , Mannose/chemistry , Molecular Structure , Ruthenium/chemistry , Stereoisomerism , Thiosugars/chemistry
18.
Carbohydr Res ; 406: 86-92, 2015 Apr 10.
Article in English | MEDLINE | ID: mdl-25681998

ABSTRACT

A highly efficient and convenient C-glycosylation method was developed using ruthenium(III) chloride for the synthesis of 2,3-unsaturated C-glycosides. Various nucleophiles such as allyl trimethylsilane, triethylsilane, trimethylsilyl cyanide, trimethylsilyl azide and heterocycles such as thiophene and furan reacted smoothly with glycals in the presence of catalytic amount of ruthenium trichloride under mild reaction conditions.


Subject(s)
Glycosides/chemical synthesis , Ruthenium/chemistry , Catalysis , Glycosylation , Stereoisomerism
19.
Viruses ; 6(6): 2287-327, 2014 Jun 06.
Article in English | MEDLINE | ID: mdl-24915458

ABSTRACT

Peste des petits ruminants (PPR) is caused by a Morbillivirus that belongs to the family Paramyxoviridae. PPR is an acute, highly contagious and fatal disease primarily affecting goats and sheep, whereas cattle undergo sub-clinical infection. With morbidity and mortality rates that can be as high as 90%, PPR is classified as an OIE (Office International des Epizooties)-listed disease. Considering the importance of sheep and goats in the livelihood of the poor and marginal farmers in Africa and South Asia, PPR is an important concern for food security and poverty alleviation. PPR virus (PPRV) and rinderpest virus (RPV) are closely related Morbilliviruses. Rinderpest has been globally eradicated by mass vaccination. Though a live attenuated vaccine is available against PPR for immunoprophylaxis, due to its instability in subtropical climate (thermo-sensitivity), unavailability of required doses and insufficient coverage (herd immunity), the disease control program has not been a great success. Further, emerging evidence of poor cross neutralization between vaccine strain and PPRV strains currently circulating in the field has raised concerns about the protective efficacy of the existing PPR vaccines. This review summarizes the recent advancement in PPRV replication, its pathogenesis, immune response to vaccine and disease control. Attempts have also been made to highlight the current trends in understanding the host susceptibility and resistance to PPR.


Subject(s)
Peste-des-Petits-Ruminants/virology , Peste-des-petits-ruminants virus/physiology , Animals , Antiviral Agents/therapeutic use , Disease Resistance , Goat Diseases , Goats , Host-Pathogen Interactions , Peste-des-Petits-Ruminants/drug therapy , Peste-des-Petits-Ruminants/epidemiology , Peste-des-Petits-Ruminants/immunology , Peste-des-Petits-Ruminants/prevention & control , Sheep , Sheep Diseases , Viral Vaccines/immunology , Virus Replication
20.
Bioorg Med Chem ; 22(7): 2253-60, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24650704

ABSTRACT

Methylation of histones by lysine methyltransferases (KMTases) plays important roles in regulating chromatin function. It is also now clear that improper KMTases activity is linked to human diseases, such as cancer. We report an approach that employs drug-like 'privileged' scaffolds biased with motifs present in S-adenosyl methionine, the cofactor used by KMTases, to efficiently generate inhibitors for Set7, a biochemically well-characterized KMTase. Setin-1, the most potent inhibitor of Set7 we have developed also inhibits the KMTase G9a. Together these data suggest that these inhibitors should provide good starting points to generate useful probes for KMTase biology and guide the design of KMTase inhibitors with drug-like properties.


Subject(s)
Enzyme Inhibitors/pharmacology , Histone-Lysine N-Methyltransferase/antagonists & inhibitors , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Histone-Lysine N-Methyltransferase/metabolism , Humans , Molecular Structure , Structure-Activity Relationship
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