Yogesh P. Bharitkar

Regio- and Stereoselective Synthesis of a Library of Bioactive Dispiro-Oxindolo/Acenaphthoquino Andrographolides via 1,3-Dipolar Cycloaddition Reaction Under Microwave Irradiation

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.

Evaluation of the wound healing activity of Shorea robusta, an Indian ethnomedicine, and its isolated constituent(s) in topical formulation.

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.

Synthesis of Bis-pyrrolizidine-Fused Dispiro-oxindole Analogues of Curcumin via One-Pot Azomethine Ylide Cycloaddition: Experimental and Computational Approach toward Regio- and Diastereoselection.

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.

Towards the Development of Anticancer Drugs from Andrographolide: Semisynthesis, Bioevaluation, QSAR Analysis and Pharmacokinetic Studies

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.

Tamarixetin 3-O-β-d-Glucopyranoside from Azadirachta indica Leaves: Gastroprotective Role through Inhibition of Matrix Metalloproteinase-9 Activity in Mice

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.

Insights of Spermicidal Research: An Update

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.

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

Summary 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.

Synthesis of diversely substituted bis-pyrrolizidino/ thiopyrrolizidino oxindolo/acenaphthyleno curcuminoids via sequential azomethine ylide cycloaddition

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.

Ultrastructural changes in Raillietina (Platyhelminthes: cestoda), exposed to sulfonoquinovosyldiacylglyceride (SQDG), isolated from Neem (Azadirachta indica)

Abstract 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.

Asiatic acid, a non-detergent type spermicide: exploration of plausible pathway of spermicidal action

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.