Inder Pal Singh

Cancer chemopreventive activity of euglobal-G1 from leaves of Eucalyptus grandis.

In the course of our continuing search for novel cancer chemopreventive agents from natural sources, several kinds of Eucalyptus plants were screened. Consequently, the phlorogrucinol-monoterpene derivative, euglobal-G1 (EG-1), was obtained from the leaves of Eucalyptus grandis as an active constituent. EG-1 exhibited the remarkable inhibitory effect on two-stage carcinogenesis test of mouse skin tumors induced by 7, 12-dimethylbenz[a]anthracene (DMBA) as an initiator and fumonisin-B1, which has been known as one of mycotoxins produced by Fusarium monifliforme, as a promoter. Further, EG-1 exhibited potent anti-tumor-promoting activity on two-stage carcinogenesis test of mouse pulmonary tumor using 4-nitroquinoline-N-oxide (4-NQO) as an initiator and glycerol as a promoter.

Five phloroglucinol-monoterpene adducts from Eucalyptus grandis

Five new euglobals possessing the phloroglucinol-monoterpene structure, euglobals G8-G12, together with a known euglobal-IIc were isolated from the hexane fraction of the methanol extract of the leaves of Eucalyptus grandis. Euglobal-G8 is an adduct of formyl-isovaleroyl-phloroglucinol and gamma-terpinene whereas -G9, -G10 and -G11 have the same phloroglucinol moiety fused with alpha-terpinene, while Euglobal-G12 has terpinolene fused with the same phloroglucinol moiety. The structures of these compounds were elucidated on the basis of spectral evidences. Biomimetic synthesis of euglobals suggests that these compounds are derived biogenetically by the Diels-Alder type cycloaddition of the corresponding terpenes with an ortho-quinone methide generated from grandinol.

Shogaols from Zingiber officinale as promising antifouling agents.

We isolated the highly potent attachment-inhibitors (three times more active than standard CuSO4 in the blue mussel assay), trans-6-, 8-, and 10-shogaols, from a hexane extract of the roots of ginger, Zingiber officinale Roscoe. Trans-8-shogaol showed the highest antifouling activity comparable with that of tributyltin fluoride (TBTF), which is recognized as one of the most effective antifouling agents, in the conventional submerged assay.

Grandinal, a New Phloroglucinol Dimer from Eucalyptus grandis

Grandinal, a new dimeric phloroglucinol compound, was isolated from Eucalyptus grandis and characterized by spectral techniques. Tautomeric structures 1, 2, and 3 were assigned to grandinal. Biogenetically, 1 is proposed to be formed from intermediates derived from grandinol and jensenone.

Structure-Activity Relationship of Phloroglucinol Compounds from Eucalyptus as Marine Antifoulants

Environmental pollution has resulted in the use of organo-tin and organo-copper compounds as antifouling agents being prohibited. Non-toxic natural products are considered to be environmentally friendly antifouling agents. Several phloroglucinol compounds isolated from three species of Eucalyptus have demonstrated strong attachment-inhibiting activity against the blue mussel. In this paper, we discuss the structure-activity relationship of these phloroglucinol compounds on the basis of molecular mechanics calculations. When these compounds were superimposed on each other and the strongest inhibitor was applied as a template, the repulsion energy of the other compounds was proportional to the logarithmic attachment-inhibiting activity. It is concluded that, of the two phloroglucinol rings in sideroxylonal A, ring C is more important, and those compounds that stereochemically and electrostatically resemble the template molecule are more active.

Macrocarpals in Eucalyptus SPP. As Attachment-Inhibitors Against the Blue Mussel

Abstract We have isolated and characterized a new macrocarpal named macrocarpal K, an isopentylphloroglucinol-β-eudesmol adduct. We have also tested six macrocarpals, including macrocarpal K for attachment-inhibiting activity against the blue mussel Mytilus edulis galloprovincialis. Macrocarpals A, B, E, am-1, H and K showed potent attachment-inhibiting activity against the blue mussel, which was 1–3 times higher than the standard antifoulant CuSO4.

Oxidative stress-induced JNK/AP-1 signaling is a major pathway involved in selective apoptosis of myelodysplastic syndrome cells by Withaferin-A

Myelodysplastic syndromes (MDS) are a diverse group of malignant clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, dysplastic cell morphology in one or more hematopoietic lineages, and a risk of progression to acute myeloid leukemia (AML). Approximately 50% of MDS patients respond to current FDA-approved drug therapies but a majority of responders relapse within 2-3 years. There is therefore a compelling need to identify potential new therapies for MDS treatment. We utilized the MDS-L cell line to investigate the anticancer potential and mechanisms of action of a plant-derived compound, Withaferin A (WFA), in MDS. WFA was potently cytotoxic to MDS-L cells but had no significant effect on the viability of normal human primary bone marrow cells. WFA also significantly reduced engraftment of MDS-L cells in a xenotransplantation model. Through transcriptome analysis, we identified reactive oxygen species (ROS)-activated JNK/AP-1 signaling as a major pathway mediating apoptosis of MDS-L cells by WFA. We conclude that the molecular mechanism mediating selective cytotoxicity of WFA on MDS-L cells is strongly associated with induction of ROS. Therefore, pharmacologic manipulation of redox biology could be exploited as a selective therapeutic target in MDS.