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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 IC50 of 17.99 ± 0.26 µg/ml which is comparable to the positive control acarbose.

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 shows an IC 50 value of 3.8 mM against aggressive, highly metastatic triple-negative breast cancer cell line MDA-MB-231.

Green chemistry is an essential part of the organic synthesis chemistry and plays a principal role in saving the environment from harmful and toxic catalysts. Fruit juice catalyzed chemistry is a vital part of green chemistry in which lemon juice plays a potential role in various organic transformations. This review article summarizes (from 2011-2020) the application and importance of lemon juice in synthetic organic transformation as well as synthesis of various type of nanoparticles and catalysts. This review article can help the researchers to develop the route for the synthesis of various scaffolds, small molecules, nanoparticles and catalysts under economical and environment friendly condition.

Semi-synthesis, the way of preparing novel bioactive molecules via modification of compounds isolated from natural sources is very much useful nowadays in the drug discovery process. The modification is based on the reaction of functional group(s) present in a natural compound. Among the examples of functional group transformation, double bond modification is also common in the literature. Several reactions like hydrogenation, cyclopropanation, epoxidation, addition reaction (halogenations, hydroxylation), Michael addition, Heck reaction, cycloaddition, dipolar cycloaddition, etc. are employed for this purpose. In this review, we have tried to gather the reactions performed with several double bond containing classes of natural products like diterpenes, xanthones, sesquiterpene exomethylene lactones, diaryl heptanoids, steroidal lactones, triterpenoids, limonoids, and alkamides. Where available, the effects of transformations on the biological activities of the molecules are also mentioned.

Aims of the study were the phytochemical investigation and chemical transformation of isolated compounds of medicinal plant listed in 'Ayurveda' like

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), ��-sitosterol (4) and from methanol extract five compounds; ��-sitosterol-3-O-��-D-glucopyranoside (5), 10-O-trans-p-Methoxycinnamoylcatalpol (6), Kaempferol-3-O-��-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.

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.

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.

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.

The spermicidal and microbicidal activity of Asiatic acid isolated from Shorea robusta resin was explored earlier using rat spermatozoa. The current investigation is aimed at examining the spermicidal efficacy of the molecule against human spermatozoa along with the plausible pathway involved in its spermicidal action. Spermicidal efficacy of Asiatic acid against human spermatozoa was evaluated in vitro by modified Sander-Cramer test and the subsequent mode of spermicidal action was assessed by (a) hypo-osmotic swelling test, (b) double fluoroprobe staining, (c) flow cytometric detection of apoptosis by fluorescein isothiocyanate-Annexin V labelling and (d) JC-1 labelling. The minimum effective concentration of the molecule against human spermatozoa was found to be 500 µg/ml which is comparable to the standard spermicide nonoxynol-9 (minimum effective concentration 550 µg/ml). The mechanistic pathway of spermicidal action of the molecule involves apoptosis rather than general cell necrosis. The molecule Asiatic acid may be explored as an ingredient for the formulation of a new generation non-detergent type microbicidal contraceptive.

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 several diversely substituted bis-pyrrolizidino/thiopyrrolizidino oxindolo/acenaphthyleno curcuminoids

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.

Dispiro andrographolide derivatives have been prepared from isatin/acenaphthoquinone, N-benzyl glycine and andrographolide via azomethine ylide cycloaddition reaction. The cytotoxic effect of the synthesized molecules has been studied against MCF-7 breast cancer cell line. The compounds induced apoptotic cell death as revealed by increased labeling with Annexin-V, decreased polarization of cell mitochondria, and increased reactive oxygen species production. Using FACS and western blot analysis, the compounds were observed to block the cell cycle at S phase. Activation of caspases 7 and 9 suggested that caspase pathways were involved in inducing apoptosis.

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 IC50 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.

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.

An inexpensive one-pot green methodology has been developed for the synthesis of thiazolo[2,3- a ]isoquinolin-4-ium derivatives by the reaction of different derivatives of isoquinoline and 2-bromoacetophenone/bromoacetonitrile with benzoyl isothiocyanate in aqueous micellar medium.

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.

Tetracyclic pyrrolidine/isoxazolidine fused pyrano[3,2-h]quinolines were synthesized via intramolecular 1,3-dipolar cycloaddition in ionic liquid. The transformations are operationally simple and environment-friendly in nature. The reaction is highly stereoselective affording exclusively the cis fused products, as deduced by the small coupling constant value (J = 4.8 Hz) between ring juncture protons which also showed clear NOESY correlation (in 5a and 5c). Confirmatory evidence came from single-crystal X-ray crystallography of 5d.

A simple and efficient one-pot three component synthesis of tetrahydropyrrolo[3′,4′:3,4]pyrrolo[2,1- a ]isoquinoline-9,11-dione derivatives has been achieved from variously substituted isoquinolines, 2-bromo acetophenone and N -aryl maleimide derivatives in an aqueous micellar medium. The synthesis represents an environmentally benign alternative to classical methods.

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.

An inexpensive one-pot green methodology has been developed for the synthesis of thiazolo[2,3- a ]isoquinolin-4-ium derivatives by the reaction of different derivatives of isoquinoline and 2-bromoacetophenone/bromoacetonitrile with benzoyl isothiocyanate in aqueous micellar medium.

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 $$^{\prime }$$ -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 $$\Delta ^{2}$$ -bond of the $$\upalpha $$ , $$\upbeta $$ -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 $$\upbeta $$ -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.

Spermicides came into existence as a method of contraception for over hundred years. Since then, investigations and developments in this field have led to more and more fruitful as well as promising results but still left enough scope for further studies. The titled article manifests a brief discussion on the development of spermicides from different natural and synthetic sources, a compilation of the promising molecules and even extracts and includes an outline of the basic physiology behind the bioactivity. Since spermicides are only one among several other methods of contraception adopted and practiced, an attempt has been made to probe the necessity and advantage of spermicides over other modes of contraception, emphasizing on the requirements and scope of future investigations in this field.

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.

Assessment of antibacterial as well as antiherpes virus activity ofsulfonoquinovosyldiacylglyceride (SQDG), a glycolipid, isolated from the leavesof Azadirachta indica has been described. Antimicrobial activity was evaluatedagainst Gram-positive, Gram-negative bacteria and herpes simplex virus.SQDG showed significant inhibitory activity against Salmonella typhi and twoisolates of Shigella dysenteriae with MIC values 32 lgml 1 , while three isolatesof Salm. typhi, Escherichia coli and Vibrio cholerae were inhibited at 64 lgml 1 and have shown zone diameter ranging from 6 2to12 3 mm. The growthkinetics study of SQDG on Salm. typhi and Sh. dysenteriae revealed that thegrowths were completely inhibited at their MIC values within 24 h ofexposure. Interestingly, SQDG inhibits herpes simplex virus (HSV) type 1 and2 with the EC 50 of 9 1 and 8 5 lgml 1 , compared with acyclovir (2 2 and2 8 lgml 1 against HSV-1 and HSV-2). The selectivity index (SI) was foundto be 12 4 against HSV-1 and 13 41 with HSV-2. Furthermore, the expressionof proinflammatory cytokines of HSV-infected and SQDG-treated macrophagesusing ELISA kit revealed that SQDG significantly downregulated theproduction of TNF-a, IL-1b, IL-12 and IL-6.IntroductionThe use of medicinal plants and their compounds as thesource of antimicrobial drugs have become more relevantnow-a-days due to the growing incidence of drug-resis-tant pathogens (Samy and Gopalakrishnakone 2010).Moreover, the incidence of recurrent herpes infection,caused by herpes simplex virus type 1 (HSV-1) and 2(HSV-2), has increased over the past decade, althoughHSV has been successfully treated with acyclovir since1970s, but its long-term use yielded drug resistance(Whitley and Roizman 2001). Thus, the antimicrobialagents constitute an important class of compounds andtherefore continue to be an attractive field in antimicro-bial therapy.The plant Azadirachta indica A. (Meliaceae) popularlyknown as neem has attracted attention of the researchersfor a long time as it is reported to have several biologicalactivities including antimalarial (Jones et al. 1994), immu-nomodulatory (Van der Nat et al. 1987), antifungal (Sund-arasivarao and Madhusudhanarao 1977), antibacterial (Raoet al. 1986) and so on. As a part of our continuous search

A facile synthesis of the title compounds (16 examples) is completed by 1,3-dipolar cycloaddition of isoquinolinium ylides to phenyl maleimide derivatives.

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.

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.

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.

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.