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Toona ciliata , a member of the Meliaceae family, is valued for its high-quality timber and medicinal potential in treating various ailments. In this study, two triterpene isomers were isolated and characterised as an inseparable mixture from its chloroform extract using chromatography and spectroscopic techniques. Despite rigorous/extensive attempts to separate these isomers, they co-crystallised in a consistent 67:33 ratio, as verified by X-ray crystallography. The structure was further confirmed by ESI-MS, HRMS, 1 H NMR, 13 C NMR, DEPT 90, DEPT 135, COSY, NOESY, HSQC, and HMBC. Additionally, four more compounds were isolated successfully, out of that lutein and dyscusin C found for the first time from this plant.

Dysoxyllum binectariferum is an important medicinal plant known for various biological activities like anti-inflammatory, CNS depressants, contraceptive, analgesic, immunomodulatory, antimalarial, antifeedant, leishmanicidal and antiviral. It is a rich source of rohitukine, a basic skeleton of flavopiridol. Phytochemical investigation of chloroform extracts of Dysoxyllum binectariferum leaves, lead to the isolation of beddomeilactone ( 1 ) and two new cycloartane type triterpenoids beddomeilactol ( 2 ) and binectarilactone-A (3 ) with modified A ring. Compounds were assessed for their in-vitro α- glucosidase inhibitory activity. Compound 1 was found to be most potent, showing IC 50 of 17.99 ± 0.26 µg/ml which is comparable to the positive control acarbose.

Parthenium hysterophorus plant has a diverse chemical profile and immense bioactive potential. It exhibits excellent pharmacological properties such as anti-cancer, anti-inflammatory, anti-malarial, microbicidal, and anti-trypanosomal. The present study aims to evaluate the anti-leishmanial potential and toxicological safety of anhydroparthenin isolated from P. hysterophorus. Anydroparthenin was extracted from the leaves of P. hysterophorus and characterized through detailed analysis of 1 H, 13 C NMR, and HRMS. Dye-based in vitro and ex vivo assays confirmed that anhydroparthenin significantly inhibited both promastigote and amastigote forms of the Leishmania donovani parasites. Both the cytotoxicity experiment and hemolytic assay revealed its non-toxic nature and safety index in the range of 10 to 15. Further, various mechanistic assays suggested that anhydroparthenin led to the generation of oxidative stress, intracellular ATP depletion, alterations in morphology and mitochondrial membrane potential, formation of intracellular lipid bodies, and acidic vesicles, ultimately leading to parasite death. As a dual targeting approach, computational studies and sterol quantification assays confirmed that anhydroparthenin inhibits the Sterol C-24 methyl transferase and Sterol 14-α demethylase proteins involved in the ergosterol biosynthesis in Leishmania parasites. These results suggest that anhydroparthenin could be a promising anti-leishmanial molecule and can be developed as a novel therapeutic stratagem against leishmaniasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Natural products possess unique and broader intricacies in the chemical space and have been essential for drug discovery. The crucial factor for drug discovery success is not the size of the library but rather its structural diversity. Although reports on the number of new structurally diverse natural products (NPs) have declined recently, researchers follow the next logical step: synthesizing natural product hybrids and their analogues using the most potent tool, diversity-oriented synthesis (DOS). Here, we use weed Parthenium hysterophorus as a source of parthenin for synthesis of novel dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione natural product hybrids of parthenin via chemo-, regio-, and stereoselective azomethine ylide cycloaddition. All synthesized compounds were characterized through a detailed analysis of one-dimensional (1D) and two-dimensional (2D) NMR and HRMS data, and the stereochemistries of the compounds were confirmed by X-ray diffraction analysis. All compounds were evaluated for their cytotoxicity against four cell lines (HCT-116, A549, Mia-Paca-2, and MCF-7), and compound 6 inhibited the HCT-116 cells with an IC 50 of 5.0 ± 0.08 μM., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Aims of the study were the phytochemical investigation and chemical transformation of isolated compounds of medicinal plant listed in 'Ayurveda' like Dolichandrone atrovirens , endemic to Indian subcontinents. From chloroform extract of D. atrovirens four compounds; Ursolic acid ( 1 ), Maslinic acid ( 2 ), Lupeol ( 3 ), β -sitosterol ( 4 ) and from methanol extract five compounds; β -sitosterol-3- O - β -D-glucopyranoside ( 5 ), 10- O - trans - p -Methoxycinnamoylcatalpol ( 6 ), Kaempferol-3- O - β -D-glucopyranoside ( 7 ), 6- O -[6"( S )-hydroxy-2",6"dimethyl-2"(E)-7"-octadienoyl] catalpol ( 8 ) and Ixoside ( 9 ) were isolated. Ixoside was used for the semi-synthetic modification via azomethine ylide cycloaddition leading to novel spiro-oxindolo-pyrrolizidine adduct. The structures of novel adducts were elucidated by analysis of IR, MS and 1 D/2D NMR data. Furthermore, to confirm the chemo selection of only one double bond, we performed density functional theory (DFT) calculation, which confirms the chemo selectivity. In addition, in-silico ADME studies and atom-additive approach based on SASA was also examined for the molecules which suggest that they may be potential future candidates for drug discovery.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

A simple and efficient protocol for the aza-Michael addition of various aromatic anilines to ring A of withaferin A has been developed. Stereoselectivity, functional group tolerance, broad substrate scope, short reaction time and moderate to high yield are the merits of the protocol. One of the synthesized compounds 11 shows an IC 50 value of 3.8 μM against aggressive, highly metastatic triple-negative breast cancer cell line MDA-MB-231., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A facile, multicomponent (MCR) atom-economic synthesis of novel spiro-oxindolo pyrrolizidine adducts of piperine has been achieved via an intermolecular 1,3-dipolar azomethine ylide cycloaddition reaction. Either of the two conjugated double bonds in piperine takes part in the reaction to produce two regioisomeric adducts in racemic form. Acenaphthoquinone, ninhydrin and different isatin derivatives were reacted with proline and piperine to afford a never before reported library of 22 compounds. The structures of the products were determined by 1D/2D NMR, mass spectral analysis and confirmed by X-ray crystallography of selected products. Chiral HPLC separation was performed to measure the specific rotation and CD spectra of the enantiomers for two racemic compounds.

A facile, atom-economic synthesis of isoxazilidino withaferin, a novel hybrid of withaferin A, has been accomplished via two-step reaction of nitrone synthesis followed by nitrone 1,3-dipolar cycloaddition. The reaction is highly chemoselective (preferential reaction only on one of the two double bonds present on withaferin A) and diastereoselective affording exclusively the cis-fused products. The structure was determined by detailed analysis of 1D, 2D NMR and mass spectral data.

Curcumin has been transformed to several diversely substituted bis-pyrrolizidino/thiopyrrolizidino oxindolo/acenaphthyleno curcuminoids via a sequential azomethine ylide cycloaddition reaction using isatins/acenaphthoquinone and proline/thioproline as the reagents. The products were separated via extensive chromatography and characterized by 1D/2D NMR and HRMS analysis., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Neem (Azadirachta indica), has been known to be a curative for various ailments and diseases in the traditional Indian medicinal system from times immemorial. A glycolipid sulfonoquinovosyldiacylglyceride (SQDG) isolated from the leaves of neem has been found to be a proactive antibacterial and antiviral agent in previous studies. The current communication pertains to the anthelmintic activity of SQDG in vitro against a model cestode Raillietina spp. The results of efficacy tests showed a paralysis time of 1.0 ± 0.1 and 0.7 ± 0.01 h, whereas death time of 1.6 ± 0.3 and 0.9 ± 0.02 h, following treatments with dosages of 0.5 and 1.0 mg/mL, respectively. The scanning electron microscopic studies showed significant and unique changes in the ultrastructure of the worms with prominent breakages and furrows on the surface.

Neem (Azadirachta indica) is a well-known medicinal and insecticidal plant. Although previous studies have reported the antiulcer activity of neem leaf extract, the lead compound is still unidentified. The present study reports tamarixetin 3-O-β-d-glucopyranoside (1) from a methanol extract of neem leaves and its gastroprotective activity in an animal model. Compound 1 showed significant protection against indomethacin-induced gastric ulceration in mice in a dose-dependent manner. Moreover, ex vivo and circular dichroism studies confirmed that 1 inhibited the enzyme matrix metalloproteinase-9 (MMP-9) activity with an IC 50 value of ca. 50 μM. Molecular docking and dynamics showed the binding of 1 into the pocket of the active site of MMP-9, forming a coordination complex with the catalytic zinc, thus leading to inhibition of MMP-9 activity.

The neem (Azadirachta indica A. Juss) is a tropical evergreen tree (Fam. Meliacae; Subfam. Melioideae) traditionally well known for its medicinal value. Beneficialt effects of different parts of neem are attributed to its biologically active principle ‘Azadirachtin’. Apart from Indian subcontinent, neem is widely used in African countries as therapeutics, preservatives and insecticides. Neem leaves, natural source of flavonoids, polyphenols, isoprenoids, sulphurous and polysaccharides, play important role in scavenging the free radical and subsequently arresting disease pathogenesis. Considerable research has gone into neem for developing cost effective and non-toxic products. The present review has compiled different phytochemicals isolated from neem leaves, methods of extraction and their therapeutic use in preventing several diseases. Here, we highlighted the mechanism of anti-inflammatory and antioxidant activity of neem leaf that underscores the disease through regulation of physiological responses. Also, multiple roles of neem leaf and commercial use of neem formulation as an alternative in paving a frontier in the field of drug discovery are discussed.

Curcumin has been transformed to racemic curcuminoids via an azomethine ylide cycloaddition reaction using isatin/acenaphthoquinone and proline as the reagents. The products were characterized by extensive 1D/2D NMR analysis and single-crystal X-ray crystallographic studies. The enantiomers of one racemic product were separated by HPLC on a Chiralcel OD-H column and were indeed confirmed by the CD spectra of the separated enantiomers.

Withaferin-A (WA) has attracted the attention of chemists as well as biologists due to its interesting structure and various bio-activities. In light of the promising biological importance of WA as well as pyrrolidine-2-spiro-3'-oxindole ring system, we became interested in the synthesis of a combined motif involving both the ring systems via the 1,3-dipolar cycloaddition of WA at Δ(2)-bond of the α,β-unsaturated carbonyl system. We now report a facile, atom-economic synthesis of novel spiro-pyrrolizidino-oxindole adducts of withaferin-A (10 compounds) via the intermolecular cycloaddition of azomethine ylides generated in situ from proline and isatins/acenaphthoquinone. The reaction is highly chemo, regio, and stereoselective affording the cis-fused products with β-orienting hydrogen. The structures were determined by 1D/2D NMR spectroscopic data analysis and unequivocally confirmed by X-ray crystallographic analysis in some cases. Bioevaluation of the compounds against six cancer lines (e.g., CHO, HepG2, HeLa, HEK 293, MDCK-II, and Caco-2) identified 4 promising potential anticancer compounds.

Aervalanata possesses various useful medicinal and pharmaceutical activities. Phytochemical investigation of the plant has now led to the isolation of a new 2α,3α,15,16,19-pentahydroxy pimar-8(14)-ene diterpenoid (1) together with 12 other known compounds identified as β-sitosterol (2), β-sitosterol-3-O-β-D-glucoside (3), canthin-6-one (4), 10-hydroxycanthin-6-one (aervine, 5), 10-methoxycanthin-6-one (methylaervine, 6), β-carboline-1-propionic acid (7), 1-O-β-D-glucopyranosyl-(2S,3R,8E)-2-[(2'R)-2-hydroxylpalmitoylamino]-8-octadecene-1,3-diol (8), 1-O-(β-D-glucopyranosyl)-(2S,3S,4R,8Z)-2-[(2'R)-2'-hydroxytetracosanoylamino]-8(Z)-octadene-1,3,4-triol (9), (2S,3S,4R,10E)-2-[(2'R)-2'-hydroxytetracosanoylamino]-10-octadecene-1,3,4-triol (10), 6'-O-(4″-hydroxy-trans-cinnamoyl)-kaempferol-3-O-β-D-glucopyranoside (tribuloside, 11), 3-cinnamoyltribuloside (12) and sulfonoquinovosyldiacylglyceride (13). Among these, six compounds (8-13) are reported for the first time from this plant. Cytotoxicity evaluation of the compounds against five cancer cell lines (CHO, HepG2, HeLa, A-431 and MCF-7) shows promising IC50 values for compounds 4, 6 and 12.

Isolation of andrographolide from Andrographis paniculata, preparation of a library of derivatives via 1,3-dipolar cycloaddition of andrographolide with azomethine ylides generated from isatin derivatives or acenaphthoquinone and seconday α-amino acids, evaluation of the anticancer potential of the products, quantitative structure activity relationship studies and pharmacokinetic parameter determination have been described. 2D QSAR studies revaled that steric effects and van der Waals interactions play major roles in the determination of antiproliferative activity of these derivatives. 3D QSAR study predicted that the benzyl substitution at N20 position may be important for higher steric interaction. Pharmacokinetic studies with two most potent analogues revealed moderate chemical stability but poor aqueous solubility, metabolic stability and permeability with significant CYP3A4 inhibition.

Phytochemical investigation of the plant Clerodendrum phlomidis Linn. F. (Lamiaceae) has now led to the isolation of two new flavonoid glycosides (1, 2) together with six known compounds identified as pectolinaringenin (3), pectolinaringenin-7-O-β-D-glucopyranoside (4), 24β-ethylcholesta-5,22E,25-triene-3β-ol (5), 24β-ethylcholesta-5,22E,25-triene-3β-O-β-D-glucopyranoside (6), (2S,3S,4R,10E)-2-[(2'R)-2'-hydroxytetracosanoylamino]-10-octadecene-1,3,4-triol (7) and andrographolide (8) mainly by spectroscopic analysis. Compounds 4 and 6-8 are reported for the first time from C. phlomidis.

A new series of pyrrolo[3',4':3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and pyrrolo[1,2-a]phenanthrolines were efficiently built up from an 8-hydroxyquinoline derivative or phenanthroline via 1,3-dipolar cycloaddition reaction involving non-stabilized azomethine ylides, generated in situ from the parent furo[3,2-h]quinoliniums/phenanthroliums, in presence of a copper(II) chloride-phenanthroline catalytic system. The methodology combines general applicability with high yields.

Unlabelled: Assessment of antibacterial as well as antiherpes virus activity of sulfonoquinovosyldiacylglyceride (SQDG), a glycolipid, isolated from the leaves of Azadirachta indica has been described. Antimicrobial activity was evaluated against Gram-positive, Gram-negative bacteria and herpes simplex virus. SQDG showed significant inhibitory activity against Salmonella typhi and two isolates of Shigella dysenteriae with MIC values 32 μg ml(-1) , while three isolates of Salm. typhi, Escherichia coli and Vibrio cholerae were inhibited at 64 μg ml(-1) and have shown zone diameter ranging from 6.2 to 12.3 mm. The growth kinetics study of SQDG on Salm. typhi and Sh. dysenteriae revealed that the growths were completely inhibited at their MIC values within 24 h of exposure. Interestingly, SQDG inhibits herpes simplex virus (HSV) type 1 and 2 with the EC50 of 9.1 and 8.5 μg ml(-1) , compared with acyclovir (2.2 and 2.8 μg ml(-1) against HSV-1 and HSV-2). The selectivity index (SI) was found to be 12.4 against HSV-1 and 13.41 with HSV-2. Furthermore, the expression of proinflammatory cytokines of HSV-infected and SQDG-treated macrophages using ELISA kit revealed that SQDG significantly downregulated the production of TNF-α, IL-1β, IL-12 and IL-6., Significance and Impact of the Study: The water-soluble metabolite sulfonoquinovosyldiacylglyceride (SQDG) isolated from Azadirachta indica (Neem) possess significant antibacterial as well as anti-HSV activity. The efficacies as well as the solubility factor of SQDG substantiate a greater attention for its use as phytotherapeutic drug for controlling microbial infections as most consumers have better acceptance of phytomedicines than synthetic drugs., (© 2013 The Society for Applied Microbiology.)

Ethnopharmacological Relevance: Different parts of Indian ethnomedicinal plant Shorea robusta is traditionally used for several ailments including wounds and burn by different tribal groups, since ages. Here we have validated, for the first time, the effectiveness and the possible mechanism of action of young leaf extracts of Shorea robusta, used by two distinct tribes of India, and its isolated compounds as a topical formulation in three wound models in rats., Materials and Methods: Bioactivity-guided study of the active extract resulted in the isolation of two known compounds. The prepared ointment containing extracts (2.5 and 5%, w/w), fractions (5% w/w) and isolated compounds (0.25% w/w) were evaluated on excision, incision and dead space wound models in rats by the rate of wound closure, period of epithelialisation, tensile strength, granulation tissue weight, hydroxyproline content and histopathology., Results: The animals treated with the extracts and fractions (5%) showed significant reduction in wound area 96.55 and 96.41% with faster epithelialisation (17.50 and 17.86), while the isolated compounds bergenin and ursolic acid heal the wound faster, but complete epithelialisation with 100% wound contraction was evident with 5% povidone-iodine group on 18th post-wounding day. Moreover, the tensile strength of incision wound, granuloma tissue weight, and hydroxyproline content was significantly increased in both the extract and compound(s) treated animals. Furthermore, the tissue histology of animals treated with the isolated compound(s) showed complete epithelialisation with increased collagenation, similar to povidone-iodine group., Conclusion: Thus, our results validated the traditional use of Shorea robusta young leaves in wound management., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: An alarming increase in global population is the root cause of poverty, malnutrition, sexually transmitted infections (STIs) and many other social problems. Microbicidal spermicides possessing dual function of contraception and STI protection can effectively combat this problem, and their development is of utmost importance at present., Study Design: A major metabolite isolated from Shorea robusta resin was spectroscopically characterized as asiatic acid. Spermicidal efficacy of the isolate was evaluated in vitro by a modified Sander-Cramer test. The mode of spermicidal action was assessed by (a) double fluoroprobe staining, (b) hypoosmotic swelling test and (c) scanning electron microscopy. Antimicrobial efficacy was assessed by disc diffusion and broth dilution methods using human isolates of bacteria (Escherichia coli ATCC 25938 and Pseudomonas aeruginosa 71) and fungus (Candida tropicalis)., Results: The minimum effective concentration of asiatic acid that induced instantaneous immobilization of rat spermatozoa in vitro was 125 mcg/mL. The mechanism of action involved disruption of sperm plasma membrane. The microbicidal efficacy was found to be moderate for vaginal pathogens, with no effect on normal vaginal flora., Conclusion: Asiatic acid possesses appreciable spermicidal and microbicidal potential and may be explored as an effective microbicidal spermicide., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Dispiro-pyrrolidino/pyrrolizidino fused oxindoles/acenaphthoquinones have been derived from andrographolide via azomethine ylide cycloaddition to the conjugated double-bond under microwave (MW) irradiation. The reactions are chemo-, stereo-, and regioselective in nature. Change in amino acid from sarcosine/N-benzyl glycine to l-proline changes the regiochemistry. A representative library of 40 compounds along with in vitro anticancer evaluation is reported.