Synthesis of a D-rhamnose branched tetrasaccharide, repeating unit of the O-chain from Pseudomonas syringae pv. Syringae (cerasi) 435

The first synthesis of a d-rhamnose branched tetrasaccharide, corresponding to the repeating unit of the O-chain from Pseudomonas syringae pv. cerasi 435, as methyl glycoside is reported. The approach used is based on the synthesis of an opportune building-block, that is the methyl 3-O-allyl-4-O-benzoyl-alpha-D-rhamnopyranoside, which was then converted into both a glycosyl acceptor and two different protected glycosyl trichloroacetimidate donors. Successive couplings of these three compounds afforded the target oligosaccharide. The reported synthesis is also useful to perform the oligomerization of the repeating unit.     

Preparation, spectral characterization, cytotoxic and thermal studies of platinum (IV) thiohydrazone complexes

Platinum (IV) complexes of type [Pt(L)₂Cl₂] [where, L=benzaldehyde-N,N-diphenyl-N-thiohydrazone (L¹), salicylaldehyde-N,N-diphenyl-N-thiohydrazone (L²), acetaphenone-N,N-diphenyl-N-thiohydrazone (L³) and cyclohexanone-N,N-diphenyl-N-thiohydrazone (L⁴)] have been synthesized. The thiohydrazones can exist as thione–thiol tautomer and coordinates as a bidentate N–S ligand. The ligands found to act in monobasic bidentate fashion. Analytical data reveals that metal to ligand stoichiometry is 1:2. The complexes have been characterized by elemental analysis, IR, mass, electronic, ¹H NMR spectroscopic studies, and TG/DTA study. Various kinetic and thermodynamic parameters like order of reaction (n), activation energy (E_a), apparent activation entropy (S^#) and heat of reaction (ΔH) have also been carried out for one complex. Cytotoxic study has also been carried out for one complex.     

The novel economical synthesis and antimicrobial activity of a trithiocarbonate derivative

The compound diethyl 2,2′-(thiocarbonyl-bis(sulfanediyl))-diacetate 4 belongs to the trithiocarbonate class containing a trithiocarbonate function group flanked by ethyl acetate. In this procedure, a novel economic synthesis route to obtain compound 4 is described. This compound proved to possess broad-spectrum antimicrobial activity both in vitro and in vivo, and could be used as a lead compound. It is worth mentioning that this compound has been patented [No. US 9,988,348 B1; date of patent: June 5, 2018].     

Synthesis of quinoline derivatives as diabetic II inhibitors and molecular docking studies

In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1–25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC₅₀ = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC₅₀values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC₅₀ = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC₅₀ = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like ¹H NMR, ¹³C NMR and ESIMS were used for characterization.     

Fused heterocyclic compounds bearing bridgehead nitrogen as potent HIV-1 NNRTIs. Part 1: Design,synthesis and biological evaluation of novel 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives

In our continuous efforts to identify novel potent HIV-1 NNRTIs, a novel class of 5,7-disubstituted pyrazolo[1,5-a]pyrimidine derivatives were rationally designed, synthesized and evaluated for their anti-HIV activities in MT4 cell cultures. Biological results showed that most of the tested compounds displayed excellent activity against wild-type HIV-1 with a wide range of EC₅₀ values from 5.98 to 0.07 μM. Among the active compounds, 5a was found to be the most promising analogue with an EC₅₀ of 0.07 μM against wild-type HIV-1 and very high selectivity index (SI, 3999). Compound 5a was more effective than the reference drugs nevirapine (by 2-fold) and delavirdine (by 2-fold). In order to further confirm their binding target, an HIV-1 RT inhibitory assay was also performed. Furthermore, SAR analysis among the newly synthesized compounds was discussed and the binding mode of the active compound 5a was rationalized by molecular modeling studies.     

Synthesis and in vitro acetylcholinesterase and butyrylcholinesterase inhibitory potential of hydrazide based Schiff bases

To discover multifunctional agents for the treatment of Alzheimer’s disease, a series of hydrazide based Schiff bases were designed and synthesized based on multitarget-directed strategy. We have synthesized twenty-eight analogs of hydrazide based Schiff bases, characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase and butyrylcholinesterase inhibition. All compounds showed varied degree of acetylcholinesterase and butyrylcholinesterase inhibition when compared with standard Eserine. Among the series, compounds 10, 3 and 24 having IC₅₀ values 4.12 ± 0.01, 8.12 ± 0.01 and 8.41 ± 0.06 μM respectively showed potent acetylcholinesterase inhibition when compared with Eserine (IC₅₀ = 0.85 ± 0.0001 μM). Three compounds 13, 24 and 3 having IC₅₀ values 6.51 ± 0.01, 9.22 ± 0.07 and 37.82 ± 0.14 μM respectively showed potent butyrylcholinesterase inhibition by comparing with eserine (IC₅₀ = 0.04 ± 0.0001 μM). The remaining compounds also exhibited moderate to weak inhibitory potential. Structure activity relationship has been established. Through molecular docking studies the binding interaction was confirmed.     

Synthesis and luminescent properties of lanthanide homoleptic mercaptothi(ox)azolate complexes: Molecular structure of Ln(mbt)3 (Ln = Eu, Er)

The thiolate complexes of rare earth metals Ln(SR)₃ (La, HSR = 2-mercaptothiazoline (1); La, HSR = 2-mercaptobenzoxazole (2); Y, La, Sm, Eu, Tb, Gd, Er, Tm, HSR = 2-mercaptobenzothiazole (3)) were synthesized in 84-97% yield by the reactions of silylamides Ln[N(SiMe₃)₂]₃ with respective thiols. The products were characterized by elemental analysis, IR and UV/Vis spectroscopy. The structures of 3(Eu) and 3(Er) were determined by single-crystal X-ray diffraction. All obtained compounds revealed efficient luminescence in the region 400-550 nm at 293 K assigned to the ligands emission. Besides, the luminescent spectra of thiolates 3 at 77 K displayed the phosphorescent band of the ligand at 550 nm and in the cases of 3(Eu) and 3(Tb) the sets of emissions bands characteristic for Eu³⁺ and Tb³⁺ ions.     

d-Glucose- and d-mannose-based antimetabolites. Part 2. Facile synthesis of 2-deoxy-2-halo-d-glucoses and -d-mannoses

Modified d-glucose and d-mannose analogs are potentially clinically useful metabolic inhibitors. Biological evaluation of 2-deoxy-2-halo analogs has been impaired by limited availability and lack of efficient methods for their preparation. We have developed practical synthetic approaches to 2-deoxy-2-fluoro-, 2-chloro-2-deoxy-, 2-bromo-2-deoxy-, and 2-deoxy-2-iodo derivatives of d-glucose and d-mannose that exploit electrophilic addition reactions to a commercially available 3,4,6-tri-O-acetyl-d-glucal.     

Synthesis and docking study of 2-phenylaminopyrimidine Abl tyrosine kinase inhibitors

Six analogs of imatinib, an Abl kinase inhibitor clinically used as a first-line therapeutic agent for chronic myeloid leukaemia (CML), have been synthesized and characterized. And their potency as Abl kinase inhibitors have been screened by a robust virtual screening method developed based on the crystal structure (PDB code 2hyy) of Abl-imatinib complex using Surflex-Docking. The docking results are consistent with the inhibitory potency of the compounds characterized by MS method. And the H-bonds between imatinib analogs and Thr315 and Met318 residues in Abl kinase are shown to be crucial for achieving accurate poses and high binding affinities for the ATP-competitive kinase inhibitors.