Katragadda Suresh Babu

Synthesis and biological evaluation of new piplartine analogues as potent aldose reductase inhibitors (ARIs)

As a continuation of our efforts directed towards the development of anti-diabetic agents from natural sources, piplartine was isolated from Piper chaba, and was found to inhibit recombinant human ALR2 with an IC(50) of 160 μM. To improve the efficacy, a series of analogues have been synthesized by modification of the styryl/aromatic and heterocyclic ring functionalities of this natural product lead. All the derivatives were tested for their ALR2 inhibitory activity, and results indicated that adducts 3c, 3e and 2j prepared by the Michael addition of piplartine with indole derivatives displayed potent ARI activity, while the other compounds displayed varying degrees of inhibition. The active compounds were also capable of preventing sorbitol accumulation in human red blood cells.

Synthesis and Insect Antifeedant Activity of Plumbagin Derivatives with the Amino Acid Moiety

A series of plumbagin derivatives (4a-4k) containing an amino acid moiety were synthesized under mild esterification conditions in excellent yields (35%-80%) and screened for their antifeedant activities in tobacco caterpillar (Spodoptera litura) and castor semilooper (Achaea janata) using a no-choice laboratory bioassay. The parent compound plumbagin lacked significant activity, but the analogues were effective in reducing feeding by two insect species. The introduction of an N-acetyl-l-amino acid side chain to the Michael adduct of plumbagin at the third position of the quinone moiety significantly increased antifeedant activity. Several of the analogues were also toxic or caused developmental abnormalities following topical administration.

Two new sesquiterpenoids from the rhizomes of Nardostachys jatamansi.

Phytochemical investigation of CHCl3:MeOH (1:1) extract from the rhizomes of Nardostachys jatamansi led to the isolation of two new sesquiterpenoids (5 and 6), along with six known compounds (1–4, 7, and 8). The structures of two new compounds were established using IR, MS, 1D, and 2D NMR techniques. In addition, all the isolates were tested for their cytotoxicities against the A549 (lung cancer), DU-145 (prostate cancer), MCF-7 (breast cancer), and SK-N-SH (neuroblastoma).

New seco-limonoids from Cipadessa baccifera: Isolation, structure determination, synthesis and their antiproliferative activities.

A comprehensive reinvestigation of chemical constituents from CHCl3-soluble extract of Cipadessa baccifera led to the isolation of two new limonoids 1, 2 together with six known compounds 3-8. Their structures were established on the basis of extensive analysis of spectroscopic (IR, MS, 2D NMR) data. Further, a series of cipaferen G (3) derivatives were efficiently synthesized utilizing Yamaguchi esterification (2, 4, 6-trichlorobenzoyl chloride, Et3N, THF, DMAP, toluene) at the C-3 position of the limonoids core, which is being reported for the first time. The anti-proliferative activity of the isolates and the synthetic analogues were studied against HeLa, PANC 1, HepG2, SKNSH, MDA-MB-231 and IMR32 cancer cells using the sulphorodamine B assay. Among the tested compounds, 13d and 13h manifested potent activity against IMR32, HepG2 cell lines with GI50 0.013 and 0.01μM, respectively.

Hemisynthesis of selected embelin analogs and investigation of their proapoptotic activity against cancer cells.

Embelin is a natural product, inhibitor of XIAP (X-chromosome-linked Inhibitor of APoptosis) with strong proapoptotic properties on cancer cells. In order to clarify the role of two OH groups on benzoquinone core, we have prepared by hemisynthesis close analogs of embelin, where these OH groups have been replaced in a systematic manner by OMe and OAc groups. Proapoptotic activities of six embelin derivatives have been studied as single agent, or in combination with TRAIL, and their abilities to interact with XIAP have been evaluated by Surface Plasmon Biacore. Our results show that these new embelin analogs have good proapoptotic properties against selected cancer cells, often higher than the natural product itself. Further, this activity is not directly mediated by XIAP. Altogether these preliminary results demonstrate that for active embelin analogs, the two OH groups are not absolutely required for anticancer activity, opening new possibilities for the design of proapoptotic derivatives in these series.

Quantification of bergenin from Mallotus philippinensis by HPTLC-MS and study on different extraction methods

A simple and accurate high-performance thin-layer chromatographic (HPTLC) method has been established for the determination of bergenin in the roots and stem-bark powder of Mallotus phillippensis. It has been reported to have a wide array of biological activities like antioxidant, anti-HIV, antiarrhythmic, hepatoprotective, anti-inflammatory and anti-microbial. Methanolic extract of the stem-bark and root powder was used for the experimental work. Separation was performed on 20 × 10 silica gel 60 F254 using ethyl acetate-methanol-acetic acid-formic acid (8:1:0.5:0.5, v/v) as mobile phase and scanned using densitometry at 284 nm. Extracts were prepared by conventional soaking, and accelerated solvent extractor (ASE) was used for the analysis. The results indicate that bergenin was found to be maximum in root ASE extract (6.0% w/w), while the minimum concentration of bergenin was found in stembark cold extract (2.9% w/w).The determination was carried out using the densitometric absorbance mode at 284 nm. The method was validated in terms of selectivity, linearity, precision, accuracy, and robustness. Additionally, peak identity was confirmed by mass spectrometry. The electron spray ionization (ESI) mass spectra showed the [M + Na]+ ions for bergenin detected at m/z 351 being acquired directly from the sample bands by an elution-based interface. By considering the validation results, the method was found to be very simple, accurate, precise, fast, and economical and can be used for routine quality control.

Simultaneous determination of bioactive compounds in Piper nigrum L. and a species comparison study using HPLC-PDA

Piper nigrum L. is a traditional medicine widely used in India for illnesses such as constipation, diarrhoea, earache, gangrene, heart disease, hernia, hoarseness, indigestion, insect bites, insomnia, joint pain, liver problems, lung disease, oral abscesses, sunburn, tooth decay and toothaches. In this study, six bioactive compounds, namely piperine (1), pellitorine (2), guineensine (3), pipnoohine (4), trichostachine (5) and piperonal (6) were quantified in different extracts of P. nigrum L. and compared with those of P. longum L. and P. chaba Hunter. To evaluate the quality of P. nigrum, a simple, accurate and precise HPLC-PDA method was developed for the simultaneous determination of the above-mentioned six compounds. The separation was achieved by Phenomenex Luna RP C18 column (150 × 4.6 mm, 5 µm, Phenomenex Inc, CA, USA) with a binary gradient solvent system of water–acetonitrile, at a flow rate of 1.0 mL min−1 and detected at 210, 232, 262 and 343 nm. All six calibration curves showed good linearity (R 2 > 0.9966). The method was reproducible with intra- and inter-day variations of less than 2% and 5%, respectively. The results demonstrated that this method is simple, reliable and suitable for the quality control of these plants.

Vapor-Phase Toxicity of Derris scandens Benth.-Derived Constituents against Four Stored-Product Pests

The vapor-phase toxicity of Derris scandens Benth.-derived constituents was evaluated against four stored-product pests ( Callosobruchus chinensis L., Sitophilus oryzae L., Rhyzopertha dominica L., and Tribolium castaneum H.) using fumigation bioassays and compared to those of commonly used insecticides. The structures of all constituents of were characterized by spectroscopic analyses [nuclear magnetic resonance (NMR) and mass spectrometry]. The sensitivity of the test insect to compounds varied with exposure time, concentration, and insect species. Over 100% mortality after 24 h was achieved with the compounds osajin (2), scandinone (5), sphaerobioside (8), and genistein (9) against all of the test insects, while laxifolin (3) and lupalbigenin (4) showed 100% mortality after 72 h against T. csataneum and R. dominica . Scandenone (1), scandenin A (6), and scandenin (7) were less effective. Among the insects, C. chinensis , S. oryzae , and R. dominica were more susceptible to the treatments, whereas T. castaneum was less susceptible. The results of fumigation tests indicated that compounds from D. scandens whole plant extract are potential candidates to control stored-product pests.

Validated High-Performance Thin-Layer Chromatographic Method for the Determination of Dibenzyl Cyclooctadiene Lignans from Schisandra grandiflora

A simple, accurate, and rapid high-performance thin-layer chromatographic (HPTLC) method has been established and validated for the simultaneous quantification of the four biologically active dibenzyl cyclooctadiene lignans, i.e., schisandrin (1), gomisin B (2), deoxyschisandrin (3), and gomisin N (4) from the hexane extract of Schisandra grandiflora (Wall.) Hook. f. & Thoms. Separation was performed on silica gel 60 F254 plates using a saturated mixture of toluene—ethyl acetate—methanol (6:1:1 v/v) as the mobile phase. Quantitation was performed using densitometric absorption—reflection mode at 225 nm. The method was validated for its selectivity, linearity, precision, and accuracy. HPTLC was hyphenated with a mass spectrometer as an additional tool for the confirmation of the markers using an interface. The developed method is simple and convenient which can be applied for the regular quality analysis of the raw plant material used in Chinese traditional herbal formulations.

Simultaneous Determination of Six Marker Compounds in Piper nigrum L. and Species Comparison Study Using High-Performance Thin-Layer Chromatography-Mass Spectrometry

The isolation and characterization of bioactive compounds from medicinal plants is usually a significant challenge in phytochemical analysis because of the natural chemical complexity of plant extracts. However, there exists a need for analytical tools which can quantitatively separate and characterize the components from these biosources with greater chromatographic selectivity and lesser analytical run times that facilitate the evaluation with enhanced separation profiles. Hyphenation of thin-layer chromatography (TLC/HPTLC) with mass spectrometry (MS) is an alternative for screening herbal extracts because of its rapid analysis and ability to aid structural characterization with powerful analytical capacity. The aim of the present study was to develop a sophisticated analytical method which utilizes HPTLC-MS coupling for the chromatographic profiling and evaluation of the therapeutically important genus Piper (Piperaceae). In this study, six marker compounds, namely, trichostachine, piperine, 4,5-dihydropiperlonguminine, guineensine, pellitorine, and sesamin were analyzed and quantified in extracts of Piper nigrum L. and compared with those of Piper longum L. and Piper chaba Hunter. All the samples tested showed similar phytochemical profiles, but the contents of the active ingredients varied. Additionally, HPTLC-MS further allowed confirming the identification of the constituents in the analyzed samples with greater chromatographic selectivity where HPTLC facilitated a selective chromatographic resolution, while MS offered an efficient characterization of the target compounds in one analytical run. The study finds a potential utility in adopting HPTLC-MS as a rapid and high throughput method for the efficient quantification and identification of marker compounds from medicinal plants.