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Isatin or 1H-indole-2,3-dione or 2,3-dioxindole is an indole derivative. Isatin and its analogs are synthetically useful substances where they may be utilized for the production of a broad range of heterocyclic molecules, which are depicting a wide reach of biological and pharmacological activities, as well as anticancer, anti-inflammatory, antiviral, anticonvulsant, anti-TB, antidiabetic, anti-microbial, antitumor, antimalarial, anti-HIV, antibacterial, anti-analgesic, and antiplasmodial activities. Isatin is a precursor for many synthesized therapeutic molecules that are amenable to pharmacological action and have excellent biological potential. Isatin has a magnificent scaffold for both the natural and synthetic construction of molecules. These molecules are being used in drug therapy such as anticancer, antibiotic, and antidepressant drugs and have many more clinical applications. Due to its privileged scaffolding, the synthetic versatility of isatin has produced many structurally diverse derivatives, including the substitution of mono-, di- and tri- substitution of the aryl rings A and those derived by derivation of isatin nitrogen and C2 and C3 carbon moieties. As a result, improving and expediting access to isatin-related molecules is a challenging study in synthetic organic chemistry.

Organelle stress and Liver injuries often occur in human immunodeficiency virus (HIV) infected patients under anti‐HIV therapies, yet few molecular off‐targets of anti‐HIV drugs have been identified in the liver. Here, we found through total RNA sequencing that the transcription of a host protease Ras converting CAAX endopeptidase 1 (RCE1) was altered in HepG2 cells treated with anti‐HIV protease inhibitors, ritonavir and lopinavir. Levels of RCE1 protein were inhibited in HepG2 and primary mouse hepatocytes and in the liver of mice treated with the anti‐HIV drugs, which were accompanied with inhibition of two potential substrates of RCE1, small GTP binding protein Rab13 and Rab18, which are with a common CAAX motif and known to regulate the ER‐Golgi traffic or lipogenesis. Neither Rce1 transcription nor RCE1 protein level was inhibited by Brefeldin A, which is known to interfere with the ER‐Golgi traffic causing Golgi stress. Knocking down Rce1 with RNA interference increased ritonavir and lopinavir‐induced cell death as well as expression of Golgi stress response markers, TFE3, HSP47 and GCP60, in both primary mouse hepatocytes and mouse liver, and deteriorated alcohol‐induced alanine aminotransferase (ALT) and fatty liver injury in mice. In addition, overexpressing Rab13 or Rab18 in primary human hepatocytes reduced partially the anti‐HIV drugs and alcohol‐induced Golgi fragmentation, Golgi stress response, and cell death injury. Conclusion: We identified a mechanism linking a host protease and its substrates, small guanosine triphosphate–binding proteins, to the anti‐HIV drug‐induced Golgi dysfunction, organelle stress response, and fatty liver injury., We have found that anti‐HIV protease inhibitors inhibit RCE1 and its substrates, Rab proteins with CAAX motif, which interfered with the endoplasmic reticulum–Golgi trafficking, leading to organelle stress responses and fatty liver injury. This study may provide a molecular basis for designing anti‐HIV drugs with less side effects in the liver.

Background Plants are the repository of variable number of valuable secondary metabolites that bears pharmacognostic and pharmacological implications having potentiality to emerge as super drugs in future. In-vivo production of these metabolites is influenced by the biotic and abiotic stresses resulting in continuous accumulation of diverse phytochemicals and their derivatives that can be useful in designing and developing potential drugs for future. The aim of the present study is to review the existence of medicinally important secondary metabolites and possible pharmacological and pharmacognostic importance of under-explored weed plant species Hyptis suaveolens (L.) Poit., to explore the potentiality of the plant for developing and designing the drugs for future. Main body of the abstract Hyptis suaveolens belonging to family Lamiaceae is the rich source of medicinally important phytochemicals like essential oils, tannins, saponins, phenols, flavonoids, terpenoids, alkaloids, and sterols. One or many of these compounds have antioxidative, anti-inflammatory, antispasmodic, anti-septic, anti-cancer, anti-ulcer, antimicrobial, antibacterial, antiviral, antifungal, anti-diabetic, anti-fertility, diaphoretics, anticutaneous, anticatarrhal, antirheumatic, anti-ulcer, gastroprotective, immunomodulatory, analgesic, and antiviral activity. Short conclusion Hyptis suaveolens contains unique terpenoid metabolites like suaveolic acid, suaveolol, methyl suaveolate, beta-sitosterol, ursolic acid, and phenolic compound like rosamarinic acid, methyl rosamarinate that have potentiality to substitute the traditional drugs as therapeutic agent against the resistant and newly emerged bacterial and viral pathogens. Pentacyclic triterpenoid, ursolic acid have been reported to have effective antiviral response against the SARS-CoV2 responsible for the present COVID-19 pandemic and HIV virus for which no effective vaccines are available till date. Ursolic acid has the ability to modulate the activity of main protease (Mpro) that is essential for processing of SARS-CoV2 replicase-transcriptase machinery needed for viral replication and particle assembly.

BACKGROUND: We previously developed enzyme nanoparticles (ENP) of alcohol metabolism. This study was to evaluate protective effects of facilitated removal of blood alcohol and/or acetaldehyde on anti-HIV drugs and alcohol-induced liver injuries. METHODS: ENP were prepared for degrading alcohol completely (ENP1) or partially into acetaldehyde (ENP2), which were applied to mice of acute binge or chronic-binge alcohol feeding in the presence of antivirals (ritonavir and lopinavir). Liver pathologies were examined to assess the protective effects of ENP. RESULTS: In the acute model, ENP1 and ENP2 reduced the blood alcohol concentration (BAC) by 41% and 32% respectively within 4 hr whereas in control without ENP, BAC was reduced only by 15%. Blood acetaldehyde concentration (BADC) was increased by 39% in alcohol fed mice treated with ENP2 comparing to control. No significant effects of the anti-HIV drugs on BAC or BADC were observed. Plasma alanine aminotransferase (ALT) and expression of liver TNFα were both significantly increased in the alcohol fed mice, which were normalized by ENP1. In the presence of the antivirals, ALT was partially reduced by ENP1 or ENP2. In the chronic model, inflammation, fatty liver and ALT were increased, which were deteriorated by the antivirals. ENP1 partially reduced BAC, BADC, ALT, and expression of inflammation markers of TNFα, F4/80 and IL-6 and lipogenic factors of ACC, LXRα and SREBP1. ENP2 reduced BAC without significant effects on ALT, inflammation or lipogenesis. Antivirals and alcohol synergistically increased expression of organelle stress markers of CHOP, sXBP-1, ATF6 and GCP60. ENP1 reduced BAC, CHOP and sXbp-1. However, no effects of ENP1 were found on ATF6 or GCP60. CONCLUSIONS: Removal of blood alcohol and acetaldehyde by the enzyme nanoparticles protects the liver against alcoholic injuries, and the protection is less effective in chronic alcohol and antiviral feeding due to additional drug-induced organelle stresses.

Phytochemicals are secondary metabolites produced by all plants in which some has medicinal uses. The comparative Qualitative and Quantitative phytochemical analysis of root extracts in aqueous, Chloroform, Ethyl acetate and ethanol extracts of Calotropis gigantea and calotropis procera Linn. were investigated. The comparative phytochemical analysis revealed the presence of alkaloids, saponins, tannins, flavonoids, terpenoids, glycosides, phenols group in varying concentrations. The comparative studies result of the above two plants gives a basis of its use in traditional medicine to manage ailments and disorders. It also contains some biologically active constituents worthy of further investigations. Keywords: Comparative, Qualitative, Quantitative, phytochemical, Calotropis gigantea and calotropis procera Â

In Withania somnifera, sterol molecules of immense medicinal value are diversified by means of glycosylation. Identifying sterol glycosyltransferases provides an imperative insight of diverse sterol modifications, thereby helping to comprehend the underlying plant mechanisms. In the present study, one of the W. somnifera sterol glycosyltransferase-4 (Ws-Sgtl4) gene was transformed into the W. somnifera leaf explant through Agrobacterium rhizogene. Transformed W. Somnifera Ws-Sgtl4 leaf explants were subjected to hairy root induction and analyzed for biomass accumulation. The analysis of Ws-Sgtl4 gene expression was performed at different time exposures with the application of salicylic acid and methyl jasmonate. The elicitation of W. somnifera hairy root expressing the Ws-Sgtl4 gene was also evaluated for the enhancement if any, in the total withanolide yield as well as the withanolides-A contents. The results suggested that Ws-Sgtl4 gene expression enhanced the production of total withanolide yield and withanolides-A in the hairy root culture of W. somnifera in the response to the elicitors.

Present investigation explores the cardiotoxicity of rosiglitazone (ROSI) using rat heart cardiomyocytes and db/db mice. In H9c2 cells, ROSI at 50 and 60 μM induced an increase in the percentage of apoptotic cells and superoxide generation, along with an increase in the expression of various subunits of NADPH oxidase and nitric oxide synthases, confirmed that ROSI-induced apoptosis in H9c2 cells is by ROS generation. The increase in the expression of the antioxidants like superoxide dismutase (SOD), catalase, glutathione reductase (GR), glutathione-S-transferase (GST), and glutathione peroxidase (GPx) further confirmed this notion. Heme oxygenase-1, having an important role in cell protection against oxidative stress, was found to be increased along with induction of nuclear translocation of NF-E2-related factor and increased protein kinase C δ expression. Moreover, in db/db mice, oral administration of ROSI (10 mg/kg) for 10 days induced an increase in serum creatinine kinase-MB, tissue antioxidants like SOD, catalase, GR, GST, GPx expression, cardiac troponin T, and inducible nitric oxide synthase protein expression strongly support the in vitro findings. Furthermore, global gene expression studies also showed the perturbation of oxidative phosphorylation, fat cell differentiation, and electron transport chain following ROSI treatment in vivo. These results suggested that ROSI-induced cardiac damage is due to accelerated apoptosis both in vitro and in vivo.

Sterol glycosyltransferases (SGTs) catalyze the transfer of sugar molecules to diverse sterol molecules, leading to a change in their participation in cellular metabolism. Withania somnifera is a medicinal plant rich in sterols, sterol glycosides and steroidal lactones. Sterols and their modified counterparts are medicinally important and play a role in adaptation of the plant to stress conditions. We have identified 3 members of SGT gene family through RACE (Rapid Amplification of cDNA Ends) in addition to sgtl1 reported earlier. The amino acid sequence deduced from the ORF's showed homology (45-67 %) to the reported plant SGTs. The expression of the genes was differentially modulated in different organs in W. somnifera and in response to external stimuli. Salicylic acid and methyl jasmonate treatments showed up to 10 fold increase in the expression of sgt genes suggesting their role in defense. The level of expression increased in heat and cold stress indicating the role of sterol modifications in abiotic stress. One of the members, was expressed in E. coli and the enzyme assay showed that the crude enzyme glycosylated stigmasterol. W. somnifera expresses a family of sgt genes and there is a functional recruitment of these genes under stress conditions. The genes which are involved in sterol modification are important in view of medicinal value and understanding stress.

A wide variety of cis-fused hexahydrocyclopenta [b] furan-4-ones (3, n=0), hexahydro-4(2H)-benzofuranones (3, n=1), and octahydrocyclohepta [b] furan-4-ones (3, n=2) can be prepared with high levels of stereocontrol by the title reaction. The scope and limitations of this powerful new method for assembling polycyclic ethers are explored in detail. Conformational analysis of potential oxabicyclo [4.4.0] decanyl, oxabicyclo [4.3.0] nonanyl, and oxabicyclo [4.2.0] octanyl cation intermediates allows the stereochemical outcome of the title reaction to be predicted

La trimethyl-2,2,4 oxathiolanne-1,3one-2 (A) est alkylee en 4 par des halogenures d'alkyle en presence de LDA/HMPT; la dimethyl-2,2,4 oxathiolanne-1,3one-2 (B) ne donne pas de produit d'alkylation. Les deux composes A et B donnent des produits d'aldolisation diastereoisomeres avec des aldehydes et cetones et des produits d'addition 1,2 ou 1,4 avec la cyclohexene-2one ou la butene-3one-2

L'exces diastereoisomere est relie a la densite d'electrons π et aux effets steriques dans l'electrophile

Alkylation of the (R)-camphor imine of tert-butyl glycinate with a variety of alkylating agents gave diastereoselectivities ranging from 0–100%. Simple alkyl halides larger than methyl give de's (diastereomeric excesses) of ca. 50% whereas those derived from allylic type systems afford de's of 75–100%. The results are best explained by invoking a transition state interaction between the π system of the alkylating agent and the imine which, for steric reasons, requires alkylation to occur from the pro-R face.

Synthese de perhydro cyclohepta- et benzo [b] furannones-4 par transposition acide des acetals derives de vinyl-1 cycloheptane- et cyclohexanediols-1,2 ou directement a partir des diols et d'un aldehyde