Synthesis and bioactivity of phosphorylated derivatives of stavudine

Novel phosphorylated derivatives of stavudine were synthesized by the reaction of bis(2-chloroethyl)phosphoramidic dichloride/4-nitrophenyl phosphorodichloridate with various cyclic amines and amino acid esters in the presence of triethylamine in dry tetrahydrofuran through the corresponding monochloride intermediates 2a-l. Further reaction of the intermediates 2a-l with stavudine in tetrahydrofuran and pyridine in the presence of triethylamine formed the title compounds 4a-l. Their structures were characterized by IR,   1H-, 13C-, 31P-NMR and mass spectral data analyses. They exhibited good antibacterial and antioxidant activities. Their bioactivity was greatly influenced by the different groups present at the phosphorus

Hunig's base catalyzed synthesis of new 1-(2,3-dihydro-1H-inden-1-yl)-3-aryl urea/ thiourea derivatives as potent antioxidants and 2HCK enzyme growth inhibitors

A series of 1-(2,3-dihydro-1H-indan-1-yl)-3-aryl urea/thiourea derivatives (4a-j) have been synthesized from the reaction of 2,3-dihydro-1H-inden-1-amine (2) with various aryl isocyanates/isothiocyanates (3a-j) by using N,N-DIPEA base (Hunig's base) catalyst in THF at reflux conditions. All of them are structurally confirmed by spectral (IR, 1H & 13C NMR and MASS) and elemental analysis and screened for their in-vitro antioxidant activity against DPPH and NO free radicals and found that compounds 4b, 4i, 4h & 4g are potential antioxidants. The obtained in vitro results were compared with the molecular docking, ADMET, QSAR and bioactivity study results performed for them and identified that the recorded in silico binding affinities were observed in good correlation with the in vitro antioxidant results. The Molecular docking analysis had unveiled the strong hydrogen bonding interactions of synthesized ligands with ARG 160 residue of protein tyrosine kinase (2HCK) enzyme and plays an effective role in its inhibition. Toxicology studies have assessed the potential risks of 4a-j and inferred that all of them were in the limits of potential drugs. The conformational analysis of 4a-j inferred that the urea/thiourea spacer linking 2,3-dihydro-1H-inden-1-amino and substituted aryl units has facilitated all these molecules to effectively bind with ARG 160 amino acid residue present on the α-helix of the protein tyrosine kinase (2HCK) enzyme specifically on chain A of hemopoetic cell kinase. Collectively this study has established a relationship between the antioxidant potentiality and ligands binding with ARG 160 amino acid residue of chain A of 2HCK enzyme to inhibit its growth as well as proliferation of reactive oxygen species in vivo

Multiple molecular targets mediated antioxidant activity, molecular docking, ADMET, QSAR and bioactivity studies of halo substituted urea derivatives of α-Methyl-l-DOPA

A series of novel α-methyl-l-DOPA urea derivatives viz., 3-(3,4-dihydroxyphenyl)-2-methyl-2-(3-halo/trifluoromethyl substituted phenyl ureido)propanoic acids (6a-e) have been synthesized from the reaction of α-methyl-l-DOPA (3) with various aryl isocyanates (4a-e) by using triethylamine (5, TEA) as a base catalyst in THF at reflux conditions. The synthesized compounds are structurally characterized by spectral (IR, 1H & 13C NMR and MASS) and elemental analysis studies and screened for their in-vitro antioxidant activity against DPPH, NO and H2O2 free radical scavenging assays and identified compounds 6c & 6d as potential antioxidants. The acquired in vitro results were correlated with the results of molecular docking, ADMET, QSAR and bioactivity studies performed for them and predicted that the recorded in silico binding affinities are in good correlation with the in vitro antioxidant activity results. The molecular docking analysis has comprehended the strong hydrogen bonding interactions of 6a-e with 1CB4, 1N8Q, 3MNG, 1OG5, 1DNU, 3NRZ, 2CDU, 1HD2 and 2HCK proteins of their respective SOD, LO, PRXS5, CP450, MP, XO, NO, PRY5 and HCK enzymes. This has sustained the effective binding of 6a-e and resulted in functional inhibition of selective aminoacid residues to be pronounced as multiple molecular targets mediated antioxidant potent compounds. In addition, the evaluated toxicology risks of 6a-e are identified with in the potential limits of drug candidates. The conformational analysis of 6c & 6d prominently infers that urea moiety uniting α-methyl-l-DOPA with halo substituted aryl units into a distinctive orientation to comply good structure-activity to inhibit the proliferation of reactive oxygen species in vivo

ZnBr2-SiO2 catalyzed green synthesis of tetrazoles: Molecular docking and antioxidant activity studies

A series of 5-substituted and 1,5-disubstituted tetrazoles were synthesized in high yields from various biologically active substituted nitriles with sodium azide under heterogeneous catalysed (ZnBr2-SiO2) [2+3] cycloaddition conditions. This reaction gave an excellent yield in the presence of catalytic amount of 0.2 g of ZnBr2-SiO2, glycerol solvent system under microwave irradiation conditions. All the prepared compounds were characterized by elemental analysis 1H NMR, 13C NMR, FT-IR, and mass spectral data. The newly synthesized compounds were investigated for their respective molecular target using molecular docking studies. The results reveal that compounds 5a, 5c, 5e and 3e have conferred with multi target property. The compounds 5a, 5c and 5e have shown the highest binding affinities of -10.1, -9.7 and -10.6 with reverse transcriptase, -8.5, -8.2 and -8.9 with Aurora B, respectively. The compounds 5a, 5e and 3e have shown -8.9, -8.5 and 8.4 with Aromatase, respectively. In addition, the antioxidant activity data reveals that all the compounds showed good antioxidant activity, particularly the compounds 3d, 5d, and 5e exhibited promising radical scavenging activity

Synthesis, spectral characterization and bioactivity evaluation of sulfonamide derivatives of p-nitrobenzene sulfonylchloride

1375-1383A simple and convenient method for the synthesis of biologically active sulfonamide derivatives of p-nitrobenzene sulfonylchloride has been achieved. All the title compounds have been characterized by spectral and elemental analysis. They have been further screened in vitro for their antibacterial and antifungal activities. All the compounds show good to moderate activity against both bacteria and fungi when compared with standard bactericide, Streptomycin and fungicide, Nystatin

First stereoselective total synthesis of (3<i style="">R</i>, 3a<i style="">S</i>, 6a<i style="">R</i>)-hexahydrofuro[2,3-<i>b</i>]furan-3-yl (2<i style="">R</i>,3<i style="">S</i>)-4-(4-amino-N-isobutyl phenylsulfonamido)-3-hydroxy-1-phenylbutan-2-yl-carbamate (diastereomer of Darunavir)

849-854The stereoselective novel synthesis of (3R,3aS,6aR)-hexahydrofuro [2,3-b]furan-3-yl (2R,3S)-4-(4-amino-N-isobutyl phenyl sulfonamido)-3-hydroxy-1-phenylbutan-2-yl-carbamate, has been accomplished in situ from the intermediate 4-amino-N-((2S,3R)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzen sulfonamide 7. This reaction gives 88% yield, with an optical purity of 99.5% and diastereomeric purity of 99% for chiral alcohol 8

Synthesis, Spectroscopic Characterization, Antimicrobial and Antioxidant Activities of Novel Phosphorylated Derivatives of Amlodipine

<div><p></p><p>A series of novel phosphorylated derivatives of Amlodipine were synthesized by the reaction of amlodipine with 2-chlorophenyl phosphorodichloridate in the presence of tetramethylguanidine in dry THF to form an intermediate product. The intermediate on further reaction with various aminoacid esters in the presence of tetramethylguanidine in dry THF afforded the title compounds. Their structures were characterized by IR, ¹H, ¹³C, ³¹P NMR, mass, and elemental analyses. All the title compounds exhibited promising antimicrobial and antioxidant activities. Their bioactivity was greatly influenced by different groups present at the phosphorus.</p></div

Synthesis and biological evaluation of novel urea and thiourea derivatives of valacyclovir

A series of novel urea and thiourea derivatives of valacyclovir were efficiently synthesized in high yields and evaluated their antiviral activity. 2-((6-Amino-4-oxo-4,5-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methoxy)ethyl-2-amino-3-ethylbutanoate (valacyclovir) 1 is reacted with various aromatic isocyanates/thiocyanates 2 in the presence of N, N- dimethyl piperazine as a base in THF: pyridine (4:1) to obtain valacyclovir urea/thiourea derivatives 3(a-j). The structures of the title compounds 3(a-j) were confirmed by IR, NMR (1H, 13C), mass spectral and elemental analysis. The newly synthesized compounds were screened for their antiviral activity against Tobacco mosaic virus (TMV) and antioxidant activity was evaluated by DPPH, SOD and GST methods. The title compounds exhibited potent antiviral and good antioxidant activities