V. Rama Subba Rao

New Labdane diterpenes as intestinal α-glucosidase inhibitor from antihyperglycemic extract of Hedychium spicatum (Ham. Ex Smith) rhizomes

Phytochemical investigation of antihyperglycemic extract of rhizomes of Hedychium spicatum led to the isolation of two new labdane type diterpenes 2, 3 along with seven known compounds (1, 4-9). Their structures were established on the basis of NMR (1D and 2D) and mass spectroscopic analysis. The new compound 2 displayed strong intestinal alpha-glucosidase inhibitory activity. Other compounds also displayed varying degree of intestinal alpha-glucosidase inhibitory potential.

Synthesis and biological evaluation of novel 8-aminomethylated oroxylin A analogues as α-glucosidase inhibitors

A series of 8-aminomethylated derivatives (1a-1j) were prepared by Mannich reaction of oroxylin A (1) with appropriate primary or secondary amines and para-formaldehyde. All the compounds were tested for their alpha-glucosidase inhibition activity against both yeast and rat intestinal alpha-glucosidase. Some of the compounds demonstrated significantly better alpha-glucosidase inhibitory activity than the parent compound (oroxylin A).

Diferuloylmethane augments the cytotoxic effects of piplartine isolated from Piper chaba.

Natural compound based anticancer drug discovery is gaining interest against a wide variety of tumors. E-piplartine (trans-piplartine), a natural compound isolated from Piper chaba roots is examined against rat histiocytoma (BC-8), mouse embryonal carcinoma (PCC4), mouse macrophages (P388D1 and J774), and human neuroblastoma (IMR32) tumor cells. While Z-piplartine (cis-piplartine) failed to induce cytotoxicity (even at higher concentrations, 50 microM), E-piplartine induced a dose-dependent cytotoxicity (2-24 microM) in different tumor cells. The combinatorial treatment of piplartine with diferuloylmethane (curcumin), an anti-inflammatory and anticancer agent, significantly enhanced the piplartine induced cytotoxicity in tumor cells. Diferuloylmethane itself is not cytotoxic at 15 microM concentration; however, potentiated the piplartine induced cytotoxicity. The tumor cell killing with piplartine is preceded by G1 cell cycle arrest, and surpassed diferuloylmethane induced G2/M arrest when used in combination. In PCC4 cells, piplartine inhibited the cell cycle progression by inactivating cdk2 and destabilizing cyclin D1, whereas diferuloylmethane combination inhibited the ERK1/2 and Raf-1 signaling in addition to the inhibition of cell cycle progression. The over expression of heat shock protein 70, Hsp70 in rat histiocytic tumor cells interfered with piplartine induced cytotoxicity, hence, a cross talk between stress response and anticancer agents is presented. Our data demonstrates the biological and medicinal importance of piplartine isolated from the roots of P. chaba, and indicates that E-piplartine may be a promising candidate to use in combinatorial treatments to combat cancer.

Synthesis and anticancer effects of pongamol derivatives on mitogen signaling and cell cycle kinases

A series of oxazole and pyrazole derivatives of pongamol (1) were designed and synthesized to examine their anti-cancer activity. The cytotoxicity of these compounds was examined in three different human tumor cell lines, IMR-32, HeLa and Jurkat. Although all compounds tested were quite effective than the pongamol against all the three different types of cancer cell lines examined, the compounds (2), (5), and (6) were found to be the most active compounds of this series.Graphical abstractA series of pongamol derivatives (2–13) (oxazole and Pyrazole derivatives) have been synthesized and tested for their anti-cancer properties against the three human tumor cell lines (IMR32, HeLa, and jurkat).

A new benzil derivative from Derris scandens: Structure-insecticidal activity study

Bioactivity-directed investigation of root extract of Derris scandens has led to the isolation and characterization of a new benzil derivative (11), along with ten known compounds (1-10). Their structures were determined on the basis of extensive spectroscopic (IR, MS, 1D and 2D NMR) data analysis and by comparison with the literature data. The insect antifeedant activity and growth inhibitory studies of these compounds were investigated against castor semilooper pest, Achaea janata using a no-choice laboratory bioassay. Several of the isolates displayed potent feeding deterrence and were also toxic or caused developmental abnormalities following topical administration. The new compound, derrisdione A was moderately active with an antifeedant index of 58.6+/-1.7% at 10microg/cm(3) against A. janata.

Mild and Efficient Michael Addition of Activated Olefins to Indoles using TBAB as a Catalyst: Synthesis of 3‐Substituted Indoles

Abstract A mild and efficient method for the synthesis of 3‐substituted indoles by treatment of activated olefins with indoles using TBAB as a catalyst afforded the corresponding products in excellent yields. The method is general for the preparation of a wide variety of 3‐substituted indoles.

Synthesis and biological evaluation of novel benzyl-substituted flavones as free radical (DPPH) scavengers and α-glucosidase inhibitors

Pharmacologically motivated natural product investigations have yielded a large variety of structurally unique lead compounds with interesting biomedical properties, but the natural roles of these molecules often remain unknown. In the present investigation, a series of benzyl substituted-flavone derivatives have been synthesized from the lead compounds and were screened against 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and α-glucosidase inhibitory properties. The resulting activity profiles of these flavone derivatives were compared for degree of similarity to the profile of 1–3. Most of the synthesized derivatives displayed potent activities when compared to the parent compounds. Maximum potencies for DPPH free radical scavenging activity were observed only in compounds containing the 4-hydroxyl substitution and 3-methoxyl group on the phenyl ring. While the 2- and 4-hydroxyl group substitutions on the phenyl ring seem to be crucial for the intestinal α-glucosidase inhibitory activity.