Indian Institute of Integrative Medicine

Isatins and their derivatives are important scaffolds in a wide range of pharmaceuticals, bioactive compounds, and functional materials. Herein we describe a new strategy for the synthesis of isatins from indoles via oxone®/TBAI-mediated oxidative dearomatization of indoles in water. The strategy works well with a variety of N-protected indoles and azaindoles.

Monarda citriodora Cerv. ex Lag. is a rich source of industrially important compounds like γ-terpinene, carvacrol, thymol and thymoquinone. Understanding the regulation of γ-terpinene biosynthesis, a precursor for other monoterpenes, could facilitate upscaling of these metabolites in M. citriodora. Therefore, the present study aimed to unravel and characterize the terpene synthase (TPS) involved in γ-terpinene biosynthesis. Homology searches revealed 33 TPS members in the transcriptome assembly of M. citriodora. Based on the correlation of expression patterns and phytochemical profile, McTPS22 emerged as the putative TPS for γ-terpinene biosynthesis. Molecular docking suggested geranyl diphosphate (GPP) as a potential substrate for McTPS22. Heterologous expression in Escherichia coli and Nicotiana benthamiana confirmed the role of McTPS22 in γ-terpinene biosynthesis. Both in-silico prediction and confocal microscopy indicated plastidial localization of the McTPS22. Gene co-expression network analysis revealed 507 genes interacting with McTPS22, including 80 transcription factors (TFs). Of these, 46 TFs had binding sites in the McTPS22 promoter, and 36 showed significant correlations with γ-terpinene accumulation, suggesting they may be potential regulators. Promoter analysis indicated regulation by phytohormones and abiotic factors, confirmed by phytohormone elicitation and QRT-PCR. The histochemical GUS staining suggested that McTPS22 is primarily active in the glandular trichomes of M. citriodora. The present work provides insights into the molecular regulation of biosynthesis of γ-terpinene in M. citriodora.

An expedient solvent free synthesis of 2-deoxy-2-bromo-hexopyrano-β-nucleosides stereo- and regioselectively from protected glycals and unactivated nucleobases using cheaper and easily available reagent systems has been developed. The synthesis was mediated...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the presence of β‐amyloid (Aβ)—containing extracellular neuritic plaques and phosphorylated tau—containing intracellular neurofibrillary tangles. It remains the primary neuropathological criteria for the diagnosis of AD. Additionally, several other processes are currently being recognized as significant risk factors for AD development, including the brain's susceptibility to reactive oxygen species (ROS). The ROS production is among the early signs in the progression of AD. However, the underlying mechanisms behind increased ROS production in AD remain poorly understood. We have observed SNTA1 plays critical role in regulating ROS levels in different pathological conditions. Here, we wanted to gain further insight into the role of SNTA1 in the development of AD by using IMR32 cell line. Our results show that the accumulation of Aβ plaques in Alzheimer's model neuroblastoma cells significantly increases the expression and activation of SNTA1 and MKK6 kinase. The activation of MKK6 results in the phosphorylation of SNTA1, creating a binding site for Rac1, leading to its activation and subsequent production of ROS. Excessive ROS production leads to cell cycle arrest in the G2/M phase, a hallmark of AD. Our study provides new insight into the mechanism of Aβ‐mediated cell death in AD and suggests that MKK6‐mediated activation of alpha‐1‐syntrophin promotes ROS production in neuronal cells, resulting in cell death. This study presents a mechanistic insight into Aβ‐mediated cell death and could serve as a paradigm for reducing neuronal cell death in AD.

A series of new oxepinyl triazoles were synthesized using labdane diterpene sclareol as a template. The synthesis process involved several steps including oxidation, oxetane ring opening, deacetylation, tosylation, and azidation followed by Huisgen’s 1,3-dipolar cycloaddition reaction with different alkynes. The newly synthesized compounds were confirmed using ¹H NMR and ¹³C NMR. These novel drimane oxepinyl triazoles derived from labdane diterpene sclareol were evaluated for their antiproliferative efficacy in colon (HCT-116), breast (MCF-7), and lung (A-549) cancer cell lines. Compound 14m demonstrated significant cytotoxic effects in all tested cell lines with an IC50 of 16 µM. Initial investigations suggested that the compound induced apoptosis and inhibited cancer cell proliferation, indicating the potential of drimane oxepinyl triazoles as promising therapeutic agents for various cancers.

To explore the rice seed microbiome, our objective was to isolate novel strains of Xanthomonas, a plant-associated bacterium with diverse lifestyles. Four isolates, anticipated to be Xanthomonas based on morphological features of yellow colonies, were obtained from healthy rice seeds. Phylo-taxono-genomic analysis revealed that these isolates formed monophyletic lineages belonging to a novel species within the genus Luteibacter. Pairwise ortho Average Nucleotide Identity and digital DNA–DNA hybridization confirmed their distinct species status. We propose Luteibacter sahnii sp. nov. as a novel species, with PPL193T = MTCC 13290T = ICMP 24807T = CFBP 9144T as the type strain and PPL201, PPL552, and PPL554 as other constituent members. The fatty acid profile of the type strain is dominated by branched fatty acids like Iso-C15:0, consistent with other members of the genus. The novel species displays non-pathogenic attributes and exhibits plant probiotic properties, protecting rice plants from the leaf blight pathogen X. oryzae pv. oryzae. Production of Indole-3-Acetic Acid (IAA) and genomic regions encoding anti-microbial peptides emphasize its potential contributions to plant hosts. This study underscores the importance of employing a combination of phenotypic and genotypic methods in culturomics to enhance our understanding of rice seed microbiome diversity.

Artemisinin‐based combinational therapies (ACTs) constitute the first line of malaria treatment. However, due to its trichome‐specific biosynthesis, low concentration, and poor understanding of regulatory mechanisms involved in artemisinin biosynthesis and trichome development, it becomes very difficult to meet the increased demand for ACTs. Here, we have reported that a bHLH transcription factor, AaMYC2‐type, plays an important role in regulating GST development and artemisinin biosynthesis in Artemisia annua . AaMYC2‐type encodes a protein that is transcriptionally active and localised to the nucleus. It is prominently expressed in aerial parts like leaves, stems, inflorescence and least expressed in roots. AaMYC2‐type expression is significantly increased under different hormonal treatments. In transgenic overexpression lines, AaMYC2‐type OE, a significant increase in the expression of trichome development and artemisinin biosynthesis genes was observed. While in knockdown lines, Aamyc2‐type , expression of trichome development and artemisinin biosynthesis genes were significantly reduced. Yeast one‐hybrid assay clearly shows that the AaMYC2‐type directly binds to the E‐boxes in the promoter regions of ADS and CYP71AVI . The SEM microscopy depicted the number of trichomes elevated from 11 mm ⁻² in AaMYC2‐type OE lines to 6.1 mm ⁻² in Aamyc2‐type . The final effect of the alteration in biosynthetic and trichome developmental genes was observed in the accumulation of artemisinin. In the AaMYC2‐type OE, the artemisinin content was 12 mg g ⁻¹ DW, which was reduced to 3.2 mg g ⁻¹ DW in the Aamyc2‐type . Altogether, the above findings suggest that the AaMYC2‐type play a dual regulating role in controlling both trichome developmental and artemisinin biosynthetic genes.

The review delves into a rich tapestry of methodologies, spanning from the utilization of metals to the manipulation of light, and from electrochemical pathways to additive‐free approaches. Its aim is to meticulously compile and elucidate these diverse pathways, providing comprehensive insights into the strategies and methodologies utilized for synthesizing these compounds. By undertaking this exploration, its goal is to shed light on the intricate techniques employed in this field, consequently driving notable progress across disciplines ranging from biochemistry to medicinal research.

Isobavachalcone (IBC) is a natural prenylated flavonoid containing chalcone and prenyl chain moieties with a wide range of biological and pharmacological properties. In this work, we synthesized structurally diversified derivatives (IBC-2 to IBC-10) from the natural prenylated chalcone IBC isolated from Psoralea corylifolia and assessed their antibacterial potency against the Gram-positive and Gram-negative bacterial strains S. aureus ATCC 29213, MRSA ATCC 15187, E. coli ATCC25922 and P. aeruginosa ATCC 27853. IBC and IBC-2 exhibited a minimum inhibition concentration (MIC) of 5.0 μM against S. aureus ATCC 29213, whereas IBC-3 exhibited a broad-spectrum activity against Gram-positive and Gram-negative pathogens. Cytotoxicity assessments on the murine RAW 264.7 macrophage cell line revealed minimal to moderate cytotoxicity for IBC-2 and IBC-3 with a favorable selectivity index (>10). Time- and concentration-dependent studies further supported the bactericidal nature of the compounds, as IBC, IBC-2, and IBC-3 exhibited concentration-dependent killing of S. aureus in a time-dependent manner. Furthermore, combination studies, SEM analysis, and PI staining suggest that IBC-3's mechanism of action targets the bacteria's cytoplasmic membrane or cell wall. The bioactive compounds displayed promising drug-like characteristics and a favorable pharmacokinetic profile (ADME-Tox), indicating a projected high oral bioavailability. Structure–activity relationships (SARs) drawn from this study reveal that a prenyl chain at the A-ring and hydroxy functional groups attached to the aromatic rings of chalcone scaffolds are responsible for this antibacterial potential, which will be helpful in the future discovery and development of antibiotics from natural products to overcome the antibiotic resistance crisis.

The present study explored the natural compound Isotelekin isolated from Inula racemose against anti‐inflammatory and immunomodulatory potential in LPS‐induced RAW264.7 cell lines and immune‐elevated SRBC‐sensitized animal models. Isotelekin in in vitro studies, inhibited the production of Th‐1 cytokines Interleukin‐6 (IL‐6), Tumour necrosis factor (TNF‐α), and Interferon‐gamma (INF‐γ), and increased Th‐2 cytokines Interleukin‐10 (IL‐10). Whereas it inhibited the nitrites and reactive oxygen species (ROS) production by mitigating the effect of LPS significantly. In vivo immunomodulatory activity in Delayed‐type hypersensitivity (DTH) and Hemagglutinating antibody (HA), Isotelekin suppressed the cellular as well as humoral immunity in immune‐affected and SRBC‐sensitized mice. Isotelekin decreased the phagocytic responses against carbon particles and plaque‐forming mainly IgG (Immunoglobulin G) production. Additionally, Isotelekin showed immunosuppressive potential through the evaluation of splenocytes, allograft acceptance, and haematological parameters. Molecular studies, including western blot analysis and immunocytochemistry, revealed that Isotelekin reduced the expression of iNOS (Inducible nitric oxide synthase), COX‐2 (Cyclo‐Oxygenase 2), and p‐IkBα (Phospho I‐kappa‐B‐alpha), and significantly inhibited the nuclear translocation of NF‐κB/p65. Based on these results, Isotelekin at 10 µm in in vitro and at 30 mg kg⁻¹ in in vivo demonstrated strong anti‐inflammatory and immunosuppressive therapeutic potential.

Nanomedicine has the potential to transform healthcare by offering targeted therapies, precise diagnostics, and enhanced drug delivery systems. The National Institutes of Health has coined the term "nanomedicine" to describe the use of nanotechnology in biological system monitoring, control, diagnosis, and treatment. Nanomedicine continues to receive increasing interest for the rationalized delivery of therapeutics and pharmaceutical agents to achieve the required response while reducing its side effects. However, as nanotechnology continues to advance, concerns about its potential toxicological effects have also grown. This review explores the current state of nanomedicine, focusing on the types of nanoparticles used and their associated properties that contribute to nanotoxicity. It examines the mechanisms through which nanoparticles exert toxicity, encompassing various cellular and molecular interactions. Furthermore, it discusses the assessment methods employed to evaluate nanotoxicity, encompassing in-vitro and in-vivo models, as well as emerging techniques. The review also addresses the regulatory issues surrounding nanotoxicology, highlighting the challenges in developing standardized guidelines and ensuring the secure translation of nanomedicine into clinical settings. It also explores into the challenges and ethical issues associated with nanotoxicology, as understanding the safety profile of nanoparticles is essential for their effective translation into therapeutic applications.

This study investigates the diverse fungal community and their probiotic functions present in ethnic fermented bamboo shoots of Arunachal Pradesh. Among 95 yeast isolates, 13 demonstrated notable probiotic attributes. These included growth at pH 3, bile tolerance, autoaggregation, co-aggregation, hydrophobicity, lysozyme tolerance and antimicrobial activity. Confirmation of some of the probiotic properties through specific primers enabled the detection of genes associated with acid and bile tolerance, antimicrobial activity, and adhesion. Probiotic yeasts were finally identified based on D1 and D2 sequences of large ribosomal subunit as Meyerozyma guilliermondii (BEP1, KGM1_3, NHR3), Meyerozyma caribbica (GEP7), Candida orthopsilopsis (ES1_2, EB1_2, EEGM2_4, GEP2, NEK9), Candida parasilopsis (HD1_1), Pichia kudriavzevii (NHR12), Pichia fermentans (BEP2), and Saccharomyces cerevisiae (NEP2). Fungal amplicon sequencing highlighted the predominance of Ascomycetes, particularly Pestalotiopsis and Penicillium genera. In this study we have perfomed a culture dependent isolation and probiotic study of yeasts and culture independent analysis of the fungal community present during the fermentation of bamboo shoots of Arunachal Pradesh which provides information about the beneficial properties of bamboo shoots as the reservoir of probiotic microorganisms.