Divergent synthesis of fractionated Cannabis sativa extract led to multiple cannabinoids C-&O-glycosides with anti-proliferative/anti-metastatic properties.

Here, we present an interesting, previously unreported method for fractionating a particular class of cannabinoids from the crude leaf extract of Cannabis sativa using HP-20 resins. In this study, we report a novel method of divergent synthesis of fractionated Cannabis sativa extract, which allows the generation of multiple cannabinoids C- and O-glycosides which react with the glycosyl donor 2,3,4,6-tetra-O-acetyl-d-mannosyl trichloroacetimidate (TAMTA) to create eight C- and O-ß-d-cannabinoids glycosides (COCG), which are separated by HPLC and whose structures are characterized by 1D, 2D NMR, and mass spectrometry. These glycosides exhibit improved anti-proliferative and anti-metastatic effects against numerous cancer cell lines in vitro and are more water-soluble and stable than their parent cannabinoids. The in vitro testing of the pure cannabinoids (1-4) and their C- & O-glycosides (1a-4a) and 1b-4b exhibited anti-proliferative and anti-metastatic activities against a panel of eight human cancer cell lines in contrast to their respective parent molecules. Different cancer cell lines' IC50 values varied significantly when their cell viability was compared. In addition to the others, compounds 2a, 3a, 4a, and 2b, 3b were highly potent, with IC50values ranging from 0.74 µM (3a) to 51.40 µM (4a).Although2a(1.42 µM) and3a(0.74 µM) exhibited lower IC50values in the MiaPaca-2 cell line than4a(2.58 µM). But, in addition to the comparable anti-clonogenic activity of4ain MiaPaca-2 and Panc-1 cells, it manifested remarkable anti-invasive activity than either 2a or 3a.In contrast to 2a, 2b, 3a, and 3b and their respective parent compounds,4ahad substantial anti-invasive/anti-metastatic capabilities and possessed anti-proliferative activity.The effects of 4a treatment on MiaPaca-2 and Panc-1 cells include a dose-dependent increase in the expression of E-cadherin and a significant decrease in the expression of Zeb-1, Vimentin, and Snail1. Our results demonstrate that divergent synthesis of fractionated Cannabis sativa extract is a feasible and efficient strategy to produce a library of novel cannabinoid glycosides with improved pharmacological properties and potential anticancer benefits.

A Secondary Metabolite of Cercospora sp., Associated with Rosa damascena Mill., Inhibits Proliferation, Biofilm Production, Ergosterol Synthesis and Other Virulence Factors in Candida albicans.

Here we describe the antimicrobial potential of secondary metabolites, fulvic acid (F.A.) and anhydrofulvic acid (AFA), produced by RDE147, an endophyte of Rosa damascena Mill. The endophyte was identified as Cercospora piaropi by ITS and ß-tubulin-based phylogenetic analyses, while chemoprofiling of the endophyte by column chromatography and spectroscopy yielded two pure compounds, F.A. and AFA. The compounds demonstrated different antimicrobial profiles, with AFA suppressing the growth of C. albicans at 7.3 µg ml-1 IC50. Further studies revealed that AFA strongly restricted the biofilm production and hyphae formation in C. albicans by down-regulating several biofilm and morphogenesis-related genes. The time-kill assays confirmed the fungicidal activity of AFA against C. albicans, killing 83.6% of the pathogen cells in 24 h at the MIC concentration, and the post-antibiotic effect (PAE) experiments established the suppression of C. albicans growth for extended time periods. The compound acted synergistically with amphotericin B and nystatin and reduced ergosterol biosynthesis by the pathogen, confirmed by ergosterol estimation and comparative expression profiling of selected genes and molecular docking of AFA with C. albicans squalene epoxidase. AFA also suppressed the expression of several other virulence genes of the fungal pathogen. The study determines the anti-C. albicans potential of AFA and its impact on the biology of the pathogen. It also indicates that Cercospora species may yield potential bioactive molecules, especially fulvic acid derivatives. However, it is imperative to conduct in vivo studies to explore this molecule's therapeutic potential further.

Bacillibactin class siderophores produced by the endophyte Bacillus subtilis NPROOT3 as antimycobacterial agents.

The bacterial endophytes isolated from the halophyte Salicornia brachiata were explored for the antimicrobial potential to discover novel microbial inhibitors that combat multidrug resistance. Upon investigation, ethyl acetate extract of the endophyte Bacillus subtilis NPROOT3 displayed significant potency against Mycobacterium smegmatis MTCC6 as well as Mycobacterium tuberculosis H37Rv strain. Further investigation of ethyl acetate crude extract by repeated chromatographic separations followed by characterization using UV, HR-ESI-MS, MALDI-MS, MALDI-MS/MS, CD, and NMR spectroscopy yielded a series of five known siderophores, namely, SVK21 (1), bacillibactin C (2), bacillibactin B (3), tribenglthin A (4), and bacillibactin (5). A total of two out of five compounds, 4 (MIC 38.66 µM) and 5 (MIC 22.15 µM) exhibited significant inhibition against the strain M. smegmatis MTCC6 comparable with positive control rifampicin (MIC 12.15 µM). None of these five bacillibactin molecules are previously reported to exhibit bioactivity against Mycobacterium sp. Herein for the first time, all the compounds were screened for their antibacterial activities against a panel of bacterial pathogens of humans. Furthermore, the probable mechanism of action of bacillibactin compounds for their antimycobacterial activity is also discussed. The findings of this study open up a new chemotype for inhibition of the Mycobacterium sp. and other multidrug-resistant pathogens.

Bacillinaphthin A: A New Naphthohydroquinone from the Endophyte Bacillus subtilis NPROOT3.

The present study explores the endophyte associated with the halophyte Salicornia brachiata for uncovering new biologically important compounds. Thus, HPLC-PDA guided chemical investigation of the ethyl acetate extract of the Bacillus subtilis NPROOT3 led to the isolation of a new compound named bacillinaphthin A (1) along with previously known rubinaphthin A (2). The structure of 2 was determined by a comparison of HR-ESI-MS, 1 H and 13 C nuclear magnetic resonances (NMR) with those of reported data, whereas the structure of new compound 1 was elucidated by interpretation of 1D- and 2D-NMR and MS data. Bacillinaphthin (1) and rubinaphthin (2) feature 1,4-dihydroxy-2-naphthoic acid derivatives which have been isolated herein for the first time from the genus Bacillus. Bacillinaphthin (1) is a new congener of 2 with an additional succinic acid side chain attached to the sugar moiety. Production of succinoglycan compounds was reported to regulate symbiosis, hence the isolation of 1 exhibits an example of chemical ecology between the halophyte and its endophyte. In silico tools were used to assess the bioactive potential of both isolated molecules.

Palladium catalyzed migratory heck coupling of arteannuin B and boronic acids: An approach towards the synthesis of antiproliferative agents in breast and lung cancer cells.

We have recently highlighting the role of spiroisoxazoline arteannuin B derivatives in mediating proinflammatory cytokines like IL-6, TNfα and NO in vitro. In the present study, a series of new ß-arylated arteannuin B analogues were synthesized through coupling with arylboroic acids and evaluated for their in vitro cytotoxic activity in a panel of six cancer cell lines. The binding efficiency was verified by docking of the original ligand within the active site of ATPase domain of GRP78 (PDB ID: 3LDL) at a resolution of 2.30 Å with the score energy of -8.07 kcal/mol. Among the new compounds 3a, 3b, 3d, 3i, 3j and 3n displayed potent cytotoxic potential with an IC50 from 2 to 18 µM and compound 3i was proven to be the most potent cytotoxic and anti-proliferative compound of all the six distinct cell lines. Compound 3i exhibited promising apoptosis inducing potential in breast cancer cells and stalled their wound healing properties and was effective in blocking the migration of cancer cells.

Site selective synthesis and anti-inflammatory evaluation of Spiro-isoxazoline stitched adducts of arteannuin B.

A library of new spiroisoxazoline analogues of arteannuin B was synthesized through 1, 3-dipolar cycloaddition in stereoselective fashion and consequently screened for anti-inflammatory activity in RAW 264.7 macrophage cells. Three potent analogues (8i, 8 m, and 8n) were found to attenuate the LPS induced release of cytokines IL-6 and TNF-α more potently than the parent molecule. Also, the inhibition of LPS induced nitric oxide production in these cells show moderate to high efficacy. None of the three potent molecules have altered the viability of RAW 264.7 cells following 48 h incubation suggesting that the inhibition of cytokines and nitric oxide production exhibited in the cells was not due to toxicity. In addition, these compounds exhibit an IC50 range of 0.17 µM-1.57 µM and 0.09 µM-0.35 µM for the inhibition of IL-6 release and nitric oxide production respectively. The results disclose potent inhibition of pro-inflammatory mediators which are encouraging and warrant further investigations to develop new therapeutic agents for inflammatory diseases.

Biodiversity and antimicrobial potential of bacterial endophytes from halophyte Salicornia brachiata.

Extreme natural habitats like halophytes, marsh land, and marine environment are suitable arena for chemical ecology between plants and microbes having environmental impact. Endophytes are an ecofriendly option for the promotion of plant growth and to serve as sustainable resource of novel bioactive natural products. The present study, focusing on biodiversity of bacterial endophytes from Salicornia brachiata, led to isolation of around 336 bacterial endophytes. Phylogenetic analysis of 63 endophytes revealed 13 genera with 27 different species, belonging to 3 major groups: Firmicutes, Proteobacteria, and Actinobacteria. 30% endophytic isolates belonging to various genera demonstrated broad-spectrum antibacterial and antifungal activities against a panel of human, plant, and aquatic infectious agents. An endophytic isolate Bacillus amyloliquefaciens 5NPA-1, exhibited strong in-vitro antibacterial activity against human pathogen Staphylococcus aureus and phytopathogen Xanthomonas campestris. Investigation through LC-MS/MS-based molecular networking and bioactivity-guided purification led to the identification of three bioactive compounds belonging to lipopeptide class based on 1H-, 13C-NMR and MS analysis. To our knowledge, this is the first report studying bacterial endophytic biodiversity of Salicornia brachiata and the isolation of bioactive compounds from its endophyte. Overall, the present study provides insights into the diversity of endophytes associated with the plants from the extreme environment as a rich source of metabolites with remarkable agricultural applications and therapeutic properties.

Analyzing the role of cannabinoids as modulators of Wnt/ß-catenin signaling pathway for their use in the management of neuropathic pain.

Neuropathic pain is a debilitating form of treatment-resistant chronic pain caused by damage to the nervous system. Cannabinoids have been known for suppressing neuropathic pain by modulating the endo cannabinoid system. Since the canonical Wnt/ß-catenin signaling has recently been implicated in pain sensation, we investigated the impact of major cannabinoids (1-6) from the leaves of Cannabis sativa and an epoxy derivative of compound 2, here upon referred to as 2a, on modulating Wnt/ß-catenin signaling pathway. The results presented in this study show that compound 1, 2 and 2a exhibited potent inhibitory activity against Wnt/ß-catenin pathway in a dose-dependent manner. Compound 2a was seen to inhibit this pathway at slightly lower concentrations than its parent molecule 2, under similar conditions. Taken together, compound 1, 2 and 2a, by virtue of their inhibition of Wnt/ß-catenin signaling pathway, could be developed as effective neuroprotective agents for the management of neuropathic pain.

Correction: Four new carbazole alkaloids from Murraya koenigii that display anti-inflammatory and anti-microbial activities.

Correction for 'Four new carbazole alkaloids from Murraya koenigii that display anti-inflammatory and anti-microbial activities' by Yedukondalu Nalli et al., Org. Biomol. Chem., 2016, 14, 3322-3332.

Porostereum sp., Associated with Saffron (Crocus sativus L.), is a Latent Pathogen Capable of Producing Phytotoxic Chlorinated Aromatic Compounds.

Saffron (Crocus sativus L.) is one of the most expensive spices in the world due to its medicinal and aromatic value. However, saffron production is severely affected by the corm rot disease throughout the saffron producing countries. In this study, we report a basidiomycetous latent pathogen of saffron, designated as CSE26, capable of producing phytotoxic compounds. CSE26 is a highly odorous basidiomycete with monomitic hyphal system. Molecular phylogeny of ITS and 28S ribosomal gene sequence of CSE26 assigned it as Porostereum spadiceum. It was found to produce corm rot in C. sativus under in vivo and field conditions, with a disease severity index of 0.7 and 0.5, respectively. CSE26 was found to produce chlorinated aromatic compounds (CAMs) having phytotoxic activity against Arabidopsis plants. Therefore, these compounds may be acting as pathogenic determinants of CSE26. However, there is a need to study the level of production of these CAMs by this fungus in the natural environment and their effects on plant health.

An Insight into the Secondary Metabolism of Muscodor yucatanensis: Small-Molecule Epigenetic Modifiers Induce Expression of Secondary Metabolism-Related Genes and Production of New Metabolites in the Endophyte.

Muscodor spp. are proficient producers of bioactive volatile organic compounds (VOCs) with many potential applications. However, all members of this genus produce varying amounts and types of VOCs which suggests the involvement of epigenetics as a possible explanation. The members of this genus are poorly explored for the production of soluble compounds (extrolites). In this study, the polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes from an endophyte, Muscodor yucatanensis Ni30, were cloned and sequenced. The PKS genes belonged to reduced, partially reduced, non-reduced, and highly reduced subtypes. Strains over-expressing PKS genes were developed through the use of small-molecule epigenetic modifiers (suberoylanilide hydroxamic acid (SAHA) and 5-azacytidine). The putative epigenetic variants of this organism differed considerably from the wild type in morphological features and cultural characteristics as well as metabolites that were produced. Each variant produced a different set of VOCs distinct from the wild type, and several VOCs including methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)hexane-2,4-diol and 2-carboxymethyl-3-n-hexylmaleic appeared in the variant strains, the production of which could be attributed to the activity of otherwise silent PKS genes. The bioactive extrolite brefeldin A was isolated and characterized from the wild type. However, this metabolite was not detected in EV-1, but instead, two other products were isolated and characterized as ergosterol and xylaguaianol C. Hence, M. yucatanensis has the genetic potential to produce several previously undetectable VOCs and organic solvent soluble products. It is also the case that small-molecule epigenetic modifiers can be used to produce stable variant strains of fungi with the potential to produce new molecules. Finally, this work hints to the prospect that the epigenetics of an endophytic microorganism can be influenced by any number of environmental and chemical factors associated with its host plant which may help to explain the enormous chemical diversity of secondary metabolic products found in Muscodor spp.

Antimicrobial Potential of Thiodiketopiperazine Derivatives Produced by Phoma sp., an Endophyte of Glycyrrhiza glabra Linn.

During the screening of endophytes obtained from Glycyrrhiza glabra Linn., the extract from a fungal culture designated as GG1F1 showed significant antimicrobial activity. The fungus was identified as a species of the genus Phoma and was most closely related to Phoma cucurbitacearum. The chemical investigation of the GG1F1 extract led to the isolation and characterization of two thiodiketopiperazine derivatives. Both the compounds inhibited the growth of several bacterial pathogens especially that of Staphylococcus aureus and Streptococcus pyogenes, with IC50 values of less than 10 µM. The compounds strongly inhibited biofilm formation in both the pathogens. In vitro time kill kinetics showed efficient bactericidal activity of these compounds. The compounds were found to act synergistically with streptomycin while producing varying effects in combination with ciprofloxacin and ampicillin. The compounds inhibited bacterial transcription/translation in vitro, and also inhibited staphyloxanthin production in S. aureus. Although similar in structure, they differed significantly in some of their properties, particularly the effect on the expression of pathogenecity related genes in S. aureus at sub-lethal concentrations. Keeping in view the antimicrobial potential of these compounds, it would be needful to scale up the production of these compounds through fermentation technology and further explore their potential as antibiotics using in vivo models.

Four new carbazole alkaloids from Murraya koenigii that display anti-inflammatory and anti-microbial activities.

In our present study, four new, designated as murrayakonine A-D (), along with 18 known carbazole alkaloids were isolated from CHCl3 : MeOH (1 : 1) crude extracts of the stems and leaves of Murraya koenigii (Linn.) Spreng. The structures of the all isolated compounds were characterized by analysis of HR-ESI-MS and NMR (1D and 2D spectroscopy) results, and comparison of their data with the literature data. For the first time, all the isolates were evaluated for their anti-inflammatory activities, using both in vitro and in vivo experiments, against the key inflammatory mediators TNF-α and IL-6. The new compound murrayakonine A (), O-methylmurrayamine A () and murrayanine () were proven to be the most active, efficiently inhibiting TNF-α and IL-6 release in a dose-dependent manner and showing decreased LPS induced TNF-α and IL-6 production in human PBMCs [corrected]. Furthermore, all the isolates were screened for their antimicrobial potential, and the compounds girinimbine () (IC50 3.4 µM) and 1-hydroxy-7-methoxy-8-(3-methylbut-2-en-1-yl)-9H-carbazole-3-carbaldehyde () (IC50 10.9 µM) displayed potent inhibitory effects against Bacillus cereus. Furthermore, compounds murrayamine J () (IC50 11.7 µM) and koenimbine () (IC50 17.0 µM) were active against Staphylococcus aureus. However, none of the compounds were found to be active against Escherichia coli or Candida albicans.

Evaluation of Anti-Inflammatory and Immunosuppressant Potential of Isotelekin in Lipopolysaccharide (LPS) Stimulated Macrophage (RAW 264.7) and Sheep Red Blood Cells (SRBC) Sensitized Murine Models.

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.

Neuroprotective Effects of Cannabispirenone A against NMDA-Induced Excitotoxicity in Differentiated N2a Cells.

The endocannabinoid system is found throughout the central nervous system, and its cannabinoids receptor 1 is critical in preventing neurotoxicity caused by N-methyl-D-aspartate receptor activation (NMDARs). The activity of NMDARs places demands on endogenous cannabinoids to regulate their calcium currents. Endocannabinoids keep NMDAR activity within safe limits, protecting neural cells from excitotoxicity. Cannabinoids are remembered to deliver this outcome by repressing presynaptic glutamate discharge or obstructing postsynaptic NMDAR-managed flagging pathways. The endocannabinoid system must exert a negative influence proportional to the strength of NMDAR signaling for such control to be effective. The goal of this paper is to draw the attention towards the neuroprotective mechanism of constituents of Cannabis sativa against NMDA-induced excitotoxic result. Phytochemical investigation of the cannabis flowers led to the isolation of nine secondary metabolites. A spiro-compound, Cannabispirenone A, which on treatment of the cells prior to NMDA exposure significantly increases cell survival while decreasing ROS production, lipid peroxidation, and intracellular calcium. Our findings showed that this compound showed neuroprotection against NMDA-induced excitotoxic insult, has antioxidative properties, and increased cannabinoid receptor 1 expression, which may be involved in the signaling pathway for this neuroprotection.

Canniprene B, a new prenylated dihydrostilbene with cytotoxic activities from the leaves of Cannabis sativa.

A new, canniprene B (4), along with five known (1-3 and 5-6) dihydrostilbenes were isolated from the leaves of Cannabis sativa collected at CSIR - IIIM, Jammu, India. Structures of all isolated compounds were elucidated by spectroscopic data analysis, including 1D and 2D NMR, and HR-ESI-MS. Canniprene B is a new prenylated dihydrostilbenes, a positional isomer of the known compound canniprene (5). The cytotoxic activities of these compounds (1-6) were evaluated using the SRB assay against a panel of five human cancer cell lines. Notably, canniprene B (4) exhibited varying levels of cytotoxicity with IC50 values ranging from 2.5 to 33.52 µM, demonstrating the most potent activity against pancreatic cancer cells.

Structural insights into the modulation Of SOD1 aggregation By a fungal metabolite Phialomustin-B: Therapeutic potential in ALS.

Amyotrophic lateral sclerosis (ALS) is a fatal human motor neuron disease leading to muscle atrophy and paralysis. Mutations in superoxide dismutase 1 (SOD1) are associated with familial ALS (fALS). The SOD1 mutants in ALS have a toxic-gain of function by destabilizing the functional SOD1 homodimer, consequently inducing fibril-like aggregation with a cytotoxic non-native trimer intermediate. Therefore, reducing SOD1 oligomerization via chemical modulators is an optimal therapy in ALS. Here, we report the discovery of Phialomustin-B, an unsaturated secondary metabolite from the endophytic fungus Phialophora mustea, as a modulator of SOD1 aggregation. The crystal structure of the SOD1-Phialomustin complex refined to 1.90 Å resolution demonstrated for the first time that the ligand binds to the dimer interface and the lateral region near the electrostatic loop. The aggregation analyses of SOD1WT and the disease mutant SOD1A4V revealed that Phialomustin-B reduces cytotoxic trimerization. We propose that Phialomustin-B is a potent lead molecule with therapeutic potential in fALS.

Canonical DDR activation by EMT inducing agent 5-Fluorouracil is modulated by a cannabinoid based combinatorial approach via inducing autophagy and suppression of vimentin expression.

Anastasis cascade including induction of Epithelial to Mesenchymal Transition (EMT), DNA repair, and stimulation of pro-survival mediators collectively exaggerate therapy resistance in cancer prognosis. The extensive implications of DNA-damaging agents are clinically proven futile for the rapid development of disease recurrence during treatment regime. Herein we report a glycosidic derivative of Δ9-tetrahydrocannabinol (THC-9-OG) abrogates sub-toxic doses of 5-Fluorouracil (5FU) induced EMT in colon cancer cells nullifying DNA repairing mechanism. Our in vitro and in vivo data strongly proclaims that THC-9-OG could not only abrogate 5FU mediated background EMT activation through stalling matrix degradation as well as murine 4T1 lung metastasis but also vigorously diminished Rad-51 repairing mediator along with stimulation of γ-H2AX foci formation. The combinatorial treatment (5FU + THC-9-OG) in Apc knockout colorectal carcinoma model conferred remission of the crypt progenitor phenotype which was prominently identified in 5FU treatment. Mechanistically, we demonstrated that 5FU plus THC-9-OG significantly attenuated major EMT inducer Vimentin via extensive ROS generation along with autophagy induction via LC3B I-II conversion and p62 degradation in a p-ATM dependent manner. Additionally, Cannabinoid receptor CB1 was responsible for abrogation of Vimentin since we found increase in the expression of γH2AX and decrease in vimentin expression in CB1 agonist (ACEA) plus 5FU treated cells. Nutshell, our results unveil a new direction of Cannabinoid based combinatorial approach to control background EMT along with robust enhancing of DNA damage potential of sub-toxic concentration of 5FU resulting immense inhibition of distant metastasis coupled with triggering cell death in vitro and in vivo.

Dactylides A-C, three new bioactive 22-membered macrolides produced by Dactylosporangium aurantiacum.

Three new 22-membered polyol macrolides, dactylides A-C (1-3), were isolated from Dactylosporangium aurantiacum ATCC 23491 employing repeated chromatographic separations, and their structures were established based on detailed analysis of NMR and MS data. The relative configurations at the stereocenters were established via vicinal 1H-1H coupling constants, NOE correlations, and by application of Kishi's universal NMR database. In order to get insights into the biosynthetic pathway of 1-3, the genome sequence of the producer strain D. aurantiacum was obtained and the putative biosynthetic gene cluster encoding their biosynthesis was identified through bioinformatic analysis using antiSMASH. Compounds 1-3 showed significant in-vitro antimycobacterial and cytotoxic activity.

Isolation, Synthesis And Structure Determination Of Cannabidiol Derivatives And Their Cytotoxic Activities.

In a continuing effort to explore the structural diversity and pharmacological activities of natural products based scaffolds, herein, we report the isolation, synthesis, and structure determination of cannabidiol and its derivatives along with their cytotoxic activities. Treatment of cannabidiol (1) with acid catalyst POCl3 afforded a new derivative 6 along with six known molecules 2 - 5, 7 and, 8. The structure of 6 was elucidated by extensive spectroscopic analyses and DFT calculations of the NMR and ECD data. All the compounds (2 - 8) were evaluated for their cytotoxic potential against a panel of eight cancer cell lines. Compounds 4, 5, 7, and 8 showed pronounced in vitro cytotoxic activity with IC50 values ranging from 5.6 to 60 µM. Out of the active molecules, compounds 4, and 7 were found to be comparable to that of the parent molecule 1 on the inhibition of almost all the tested cancer cell lines.