Air Induced Phosphoryl Radical Mediated Stereoselective Hydrosulfonylation of Alkynes via Halogen Atom Transfer: Ingress of Z-Vinyl Sulfones.

The phosphoryl radical is well-known to participate in addition reactions with alkenes/alkynes. Here, we report a novel reaction mode of the phosphoryl radical where it participates in halogen atom transfer (XAT) with electron deficient vinyl halides instead of a facile addition reaction. Nevertheless, in comparison with aryl and alkyl halides, the exploitation of vinyl halides into a carbon radical via XAT is quite rare. This protocol provides an opportunity for direct hydrosulfonylation of numerous internal as well as terminal alkynes to get various Z-vinyl sulfones under environmentally benign conditions. Generation of the phosphoryl radical in the open air, water as a solvent, excellent functional group compatibility, and exceptional chemoselectivity are the attractive features of the present methodology.

Regiodivergent Synthesis of Densely Functionalized Indolizines via (2 + 2 + 1) Cycloaddition.

A novel metal and additive free, atom-economic method for the regiodivergent synthesis of crucial 6- or 8-substituted indolizine from meta-amide-substituted pyridine and alkyne via a [2 + 2 + 1] cycloaddition is developed. The reaction proceeds through the cleavage of the carbon-carbon triple bond. The synthesized product contains an important amide group that can be further functionalized to afford biologically active compounds.

Omicron BA.2 lineage predominance in severe acute respiratory syndrome coronavirus 2 positive cases during the third wave in North India.

Background: Recent studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveal that Omicron variant BA.1 and sub-lineages have revived the concern over resistance to antiviral drugs and vaccine-induced immunity. The present study aims to analyze the clinical profile and genome characterization of the SARS-CoV-2 variant in eastern Uttar Pradesh (UP), North India. Methods: Whole-genome sequencing (WGS) was conducted for 146 SARS-CoV-2 samples obtained from individuals who tested coronavirus disease 2019 (COVID-19) positive between the period of 1 January 2022 and 24 February 2022, from three districts of eastern UP. The details regarding clinical and hospitalized status were captured through telephonic interviews after obtaining verbal informed consent. A maximum-likelihood phylogenetic tree was created for evolutionary analysis using MEGA7. Results: The mean age of study participants was 33.9 ± 13.1 years, with 73.5% accounting for male patients. Of the 98 cases contacted by telephone, 30 (30.6%) had a travel history (domestic/international), 16 (16.3%) reported having been infected with COVID-19 in past, 79 (80.6%) had symptoms, and seven had at least one comorbidity. Most of the sequences belonged to the Omicron variant, with BA.1 (6.2%), BA.1.1 (2.7%), BA.1.1.1 (0.7%), BA.1.1.7 (5.5%), BA.1.17.2 (0.7%), BA.1.18 (0.7%), BA.2 (30.8%), BA.2.10 (50.7%), BA.2.12 (0.7%), and B.1.617.2 (1.3%) lineages. BA.1 and BA.1.1 strains possess signature spike mutations S:A67V, S:T95I, S:R346K, S:S371L, S:G446S, S:G496S, S:T547K, S:N856K, and S:L981F, and BA.2 contains S:V213G, S:T376A, and S:D405N. Notably, ins214EPE (S1- N-Terminal domain) mutation was found in a significant number of Omicron BA.1 and sub-lineages. The overall Omicron BA.2 lineage was observed in 79.5% of women and 83.2% of men. Conclusion: The current study showed a predominance of the Omicron BA.2 variant outcompeting the BA.1 over a period in eastern UP. Most of the cases had a breakthrough infection following the recommended two doses of vaccine with four in five cases being symptomatic. There is a need to further explore the immune evasion properties of the Omicron variant.

Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in four malaria endemic states of India.

BACKGROUND: Malaria is a major public health problem in India and accounts for about 88% of malaria burden in South-East Asia. India alone accounted for 2% of total malaria cases globally. Anti-malarial drug resistance is one of the major problems for malaria control and elimination programme. Artemether-lumefantrine (AL) is the first-line treatment of uncomplicated Plasmodium falciparum in north eastern states of India since 2013 after confirming the resistance against sulfadoxine-pyrimethamine. In the present study, therapeutic efficacy of artemether-lumefantrine and k13 polymorphism was assessed in uncomplicated P. falciparum malaria. METHODS: This study was conducted at four community health centres located in Koraput district of Odisha, Bastar district of Chhattisgarh, Balaghat district of Madhya Pradesh and Gondia district of Maharashtra state. Patients with uncomplicated P. falciparum malaria were administered with fixed dose combination (6 doses) of artemether-lumefantrine for 3 days and clinical and parasitological response was recorded up to 28 days as per World Health Organization protocol. Nucleotide sequencing of msp1 and msp2 gene was performed to differentiate between recrudescence and reinfection. Amplification and sequencing of k13 propeller gene region covering codon 450-680 was also carried out to identify the polymorphism. RESULTS: A total 376 malaria patients who fulfilled the enrolment criteria as well as consented for the study were enrolled. Total 356 patients were followed up successfully up to 28 days. Overall, the adequate clinical and parasitological response was 98.9% and 99.4% with and without PCR correction respectively. No case of early treatment failure was observed. However, four cases (1.1%) of late parasitological failure were found from the Bastar district of Chhattisgarh. Genotyping of msp1 and msp2 confirmed 2 cases each of recrudescence and reinfection, respectively. Mutation analysis of k13 propeller gene showed one non-synonymous mutation Q613H in one isolate from Bastar. CONCLUSIONS: The study results showed that artemether-lumefantrine is highly effective in the treatment of uncomplicated P. falciparum malaria among all age groups. No functional mutation in k13 was found in the study area. The data from this study will be helpful in implementation of artemether-lumefantrine in case of treatment failure by artesunate plus sulfadoxine-pyrimethamine.

Hexadecylated linear PEI self-assembled nanostructures as efficient vectors for neuronal gene delivery.

Development of efficient and safe nucleic acid carriers is one of the most challenging requirements to improve the success of gene therapy. Here, we synthesized a linker, 3-(hexadecyloxy)-1-chloropropan-2-ol, and grafted it onto linear polyethylenimine in varying amounts to obtain a series of HD-lPEI polymers that were able to form self-assembled nanoparticles (SN). 1H-NMR spectrometry was used to determine the extent of grafting of the linker, HD, on to the lPEI backbone. We further complexed the SN of HD-lPEI with plasmid DNA (pDNA) and the resultant nanoplexes were characterized by their size and zeta potential and further evaluated for their transfection ability and cytotoxicity in MCF-7 cells. In the series, the SN of HD-lPEI-3 (ca. 15% substitution) showed the highest transfection efficiency (~ 91%) with non-significant cytotoxicity in comparison to the commercial transfection reagents. The in vitro gene knockdown study displayed ~ 80% suppression of GFP gene expression by SN of HD-lPEI-3/pDNA/siRNA complex, whereas Lipofectamine™/pDNA/siRNA complex could suppress the expression by only ~ 48%. The enhanced expression of luciferase gene using SN of HD-lPEI-3 in different vital organs of Balb/c mice also demonstrated the potential of the projected formulation for gene delivery. The encouraging results of SN of HD-lPEI-3 polymer for delivery of nucleic acids in vitro and in vivo paved the way to evaluate the potential of the same for neuronal siRNA delivery. The safe and efficient stereotaxic delivery of FITC-labeled siRNA against α-synuclein gene also confirms the potential applicability of HD-lEPI-3 SN as a vector for neuronal delivery.

Association between children death and consumption of Cassia occidentalis seeds: clinical and experimental investigations.

Recently, children with high mortality rate have been observed in northern parts of India, for which the etiology is still not established, although a case control study has been linked to the consumption of Cassia occidentalis (CO) seeds. In the present investigation toxicity of CO seeds (0.5, 1 and 2% w/w) in diet were carried out in wistar rats. After 28 days it was observed that CO seeds caused significant increases in the serum markers viz transaminases, alkaline phosphatase and lactate dehydrogenase along with histopathological lesions in hepatic tissue. CO consumption also showed decrease in grip strength, vacuolization and myopathy of skeletal muscles along with increases in serum creatinine and creatinine phosphokinase suggesting muscular damage in animals. Neuronal damage in CO treated animals was evident by a marked increase in glial fibrilar acidic protein and decrease in ß-tubulin III. The experimental findings of CO consumption showed liver, muscles and brain to be the target organs, which were similar to that of the clinical data of poisoning cases as observed in the present study. Overall, the study suggests that CO seed consumption is the main etiological factor in children population suffering from hepatomyoencephalopathy in India.