R. Ranga 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.

New furanoflavanoids, intestinal α-glucosidase inhibitory and free-radical (DPPH) scavenging, activity from antihyperglycemic root extract of Derris indica (Lam.)

A bioassay-guided fractionation and chemical examination of antihyperglycemic root extract of Derris indica resulted in isolation and characterization of two new furanoflavanoids (1, 2) along with thirteen known compounds (3-15). 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. All the compounds were tested in vitro for intestinal alpha-glucosidase inhibitory and DPPH radical activity. New compounds (1, 2) displayed moderate intestinal alpha-glucosidase inhibitory as well as free radical scavenging activity. Other compounds also displayed varying degrees of moderate intestinal alpha-glucosidase inhibitory activity. Pongamol (6) displayed potent intestinal alpha-glucosidase inhibition.

Two new cytotoxic diterpenes from the rhizomes of Hedychium spicatum.

Phytochemical investigation of CHCl(3) extract of the rhizomes of Hedychium spicatum led to the isolation of two new labdane-type diterpenes, compounds 1 and 2 along with five known compounds (3-7). Their structures were established on the basis of NMR (1D and 2D) and mass spectroscopic analysis. In addition, all the isolates were tested for their cytotoxicity against the Colo-205 (Colo-cancer), A-431 (skin cancer), MCF-7 (breast cancer), A-549 (lung cancer) and Chinese hamster ovary cells (CHO). Two new compounds 1 and 2 were shown good cytotoxic activity.

Phytochemical investigation of labdane diterpenes from the rhizomes of Hedychium spicatum and their cytotoxic activity.

A comprehensive reinvestigation of chemical constituents from the rhizomes of Hedychium spicatum led to the isolation of two new labdane-type diterpene (1, 2), together with six known compounds (3-8). Their structures were established on the basis of extensive spectroscopic (IR, MS, 2D NMR) data analysis and by comparison with the spectroscopic data reported in the literature. In addition, all the isolates were tested for their cytotoxicity against the THP-1 (human acute monocytic leukemia), HL-60 (human promyelocytic leukemia), A-375 (human malignant melanoma) and A-549 (human lung carcinoma) cancerous cell lines.

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).

Synthesis of antihyperglycemic, α-glucosidase inhibitory, and DPPH free radical scavenging furanochalcones

A series of furanochalcone derivatives have been designed and synthesized. Molecular modeling studies were carried out to probe into the mechanism of binding of chalcone inhibitors and understand the structure–activity relationship to identify the contribution of scaffolds and groups in the synthesized analogs to biological activity. The three-dimensional model of α-glucosidase was constructed based on the crystal structure family 31 α-glycosidase (PDB 1XSI) using Modeller9v5. Docking of the inhibitors on the built homology model revealed interactions in the active site region mostly with Asp 252, Tyr254, Gln523, and Arg571. 2D-QSAR models were generated with CODESSA using Heuristic method. The best predictive model was generated using three descriptors that gave a correlation co-efficient (r2) 0.9886 and cross-validate (r2) 0.9338. The synthesized compounds were screened against the α-glucosidase inhibition and DPPH radical scavenging properties. All the synthetic compounds displayed varying degrees of α-glucosidase inhibitory and DPPH scavenging activities. Compound 8c was found most potent α-glucosidase inhibitor though; it could not display DPPH scavenging activity. When tested in vivo for antihyperglycemic activity in starch-loaded Wistar rats, 8c was equally effective in reducing time-dependent hyperglycemia as to the standard drug, Acarbose. Compound 8c may serve as an interesting compound for the development of therapeutics targeted against diet-induced hyperglycemia in diabetes.

Synthesis, cytotoxic activity and structure–activity relationships of hedychenone analogues

Hedychenone, a plant-derived labdane diterpenoid, showed potent in vitro cytotoxic activity against cancerous cells. In the present study, a series of analogues have been synthesized by modification of the furanoid ring, double bond and the vinylic methyl functionality of this natural product lead and evaluated for their cytotoxic activities against human cancer cell lines. The structures of the target compounds were established by IR, (1)H NMR and mass spectral analysis. Majority of the analogues displayed potent activity than the parent compound, hedychenone. Preliminary structure-activity relationship studies indicated that furanoid ring has a greater impact on cytotoxicity than that of the decalone nucleus. However, dimerization through C-8 significantly enhanced the cytotoxic activity of the hedychenone.

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).

Synthesis and insect antifeedant activity of plumbagin derivatives

Napthaquinones have received considerable interest in agricultural chemistry because of a novel action mode, extremely high activity against a broad spectrum of insects, low acute toxicity to mammals, and environmentally benign characteristics. A series of plumbagin derivatives (3a–3o) were synthesized under mild esterification conditions in straightforward procedure. The structures of all new compounds were confirmed by NMR, IR, MS, and HREIMS analyses. The plumbagin derivatives were screened for their insecticidal activities against tobacco caterpillar (Spodoptera litura) and castor semilooper (Achaea janata) using a no-choice laboratory bioassay. The results show that some of the title compounds exhibit excellent antifeedant activities against 3rd instar larvae of A. janata and S. litura. The improvement in antifeedant activity requires a reasonable combination of substituents in the parent structure, which provides some hints for further investigation on structure modification.Graphical AbstractA series of plumbagin derivatives (3a–3o) were synthesized under mild conditions and screened for their insecticidal activities against tobacco caterpillar (Spodoptera litura) and castor semilooper (Achaea janata) using a no-choice laboratory bioassay.

New advanced glycation end-products inhibitors from Dichrostachys cinerea Wight & Arn.

Free radical scavenging and advanced glycation end-product (AGE) inhibitory potential were evaluated in the crude methanol extract of Dichrostachys cinerea. Bioassay-guided isolation led to the identification of four flavan-3-ols, namely (−)-mesquitol (1), oritin (2), (−)-festidinol (3) and (−)-epicatechin (4). Analysis of structure–activity relationships revealed that the presence of 7,8-dihydroxyl groups in the A-ring of flavan-3-ols in conjunction with 3′,4′-dihydroxyls in the B-ring (1) is an important criterion for displaying potent AGE inhibitory activity along with free radical scavenging properties. (−)-Mesquitol (1), oritin (2), and (−)-festidinol (3) were found to be new natural AGE inhibitors. (−)-Mesquitol (1) displayed the most potent AGE inhibitory activity. Results suggest that (−)-mesquitol (1) may serve as an important natural organic lead compound for future development of antiglycating agents along with potent antioxidant activity.