Che Puteh Osman

UV/Visible spectra of a series of natural and synthesised anthraquinones: experimental and quantum chemical approaches

Root decoctions of anthraquinone-containing plants are often taken as postpartum tonic and aphrodisiac. Anthraquinones are known for their diverse biological activities, especially antioxidant and anticancer. A series of 35 anthraquinones was generated by isolation from Rubiaceae plants and synthesis. Their UV/vis spectrum depends on the nature and relative positions of auxochromic substituents on the basic skeleton. To predict the maximum absorption bands for the current series of anthraquinones, excited sate calculations were performed using TD-DFT, CIS, ZINDO methods. The results showed that the use of PBE0 or its combination with B3LYP and B3P86 hybrid functionals are the most suitable to reproduce accurately the experimental λMAX. The structure–property relationships (SPRs) were established based on structural and electronic properties of the anthraquinones and showed (i) the importance of the number and position of OH groups and (ii) the positive contribution of the electrophilicity and hardness as electronic descriptors on position and amplitude of the maximum absorption bands.

Nordamnacanthal potentiates the cytotoxic effects of tamoxifen in human breast cancer cells

Tamoxifen (TAM) is the mainline drug treatment for breast cancer, despite its side effects and the development of resistance. As an alternative approach, in the present study a novel combination therapy was established through combining TAM with nordamnacanthal (NDAM) in order to investigate the additive effect of these drugs in MCF-7 human breast cancer cells. A significant dose-dependent reduction in cell viability and an increase in apoptosis were observed in the MCF-7 cells cotreated with TAM and NDAM compared with the untreated control cells or the cells treated with TAM and NDAM alone (P<0.05). The cytotoxic influence of the combination of TAM and NDAM was found to be two-fold that of the individual agents. Annexin V/propidium iodide double-staining revealed the typical nuclear features of apoptosis. Furthermore, an increase in the proportion of apoptotic, Annexin V-positive cells was observed with the combination therapy. Moreover, this apoptotic induction was associated with a collapse of the mitochondrial membrane potential and the generation of reactive oxygen species. To the best of our knowledge, the findings of the present study are the first to suggest that combining TAM with NDAM may be a potential combination therapy for the treatment of breast cancer and may have the potential to minimize or eliminate the side effects associated with high doses of TAM.

Alkaloids and Anthraquinones from Malaysian Flora

The flora of Malaysia is one of the richest flora in the world due to the constantly warm and uniformly humid climate. Malaysia is listed as 12th most diverse nation (Abd Aziz, 2003) in the world and mainly covered by tropical rainsforests. Tropical rainforests cover only 12% of earth’s land area; however they constitute about 50% to 90% of world species. At least 25% of all modern drugs originate from rainforests even though only less than 1% of world’s tropical rainforest plant species have been evaluated for pharmacological properties (Kong, et al., 2003). The huge diversity of Malaysian flora with about 12 000 species of flowering plants offers huge chemical diversities for numerous biological targets. Malaysian flora is a rich source of numerous class of natural compounds such as alkaloids, anthraquinones and phenolic compounds. Plants are usually investigated based on their ethnobotanical use. The phytochemical study of several well-known plants in folklore medicine such as Eurycoma longifolia, Labisia pumila, Andrographis paniculata, Morinda citrifolia and Phyllanthus niruri yielded many bioactive phytochemicals. This review describes our work on the alkaloids of Fissistigma latifolium and Meiogyne virgata from family Annonaceae and anthraquinones of Renellia and Morinda from Rubiaceae family.

1-Hydr­oxy-2-meth­oxy-6-methyl-9,10-anthraquinone from Rennellia elliptica Korth.

The title compound, C16H12O4, exists as planar molecules in the solid state (r.m.s. deviation of 0.02 Å in one molecule and 0.07 Å in the second independent molecule comprising the asymmetric unit). In each molecule, the 1-hydroxy group forms an intramolecular hydrogen bond to the adjacent carbonyl O atom.

Prelimanary Quantitative Structure-Activity Relationship Study of 9,10- Anthraquinone Analogues Based on their Antiplasmodial Activity

Anthraquinones isolated from the roots of Rennellia elliptica Korth. demonstrated interesting antiplasmodial activity. In addition, a series of 9,10-anthraquinones resembling those isolated from R. elliptica were synthesized and preliminary two dimensional quantitative SAR (2D-QSAR) study was performed to examine physico-chemical properties essential for antiplasmodial activity of 9,10-anthraquinones. The analogues of bioactive natural anthraquinones were synthesized through Friedel-Craft reaction between phthalic anhydride and various benzene derivatives in the presence of eutectic mixture of aluminium chloride and sodium chloride. The antiplasmodial activity was determined based on inhibition of the compounds against Plasmodium falciparum (3D7) growth in vitro. The 2D-QSAR models were developed using 24 anthraquinones as data set using Vlife MDS 3.5 software. Multiple linear regression (MLR) and principal component regression (PCR) methods were used coupled with various feature selection methods i.e. stepwise forward, stepwise forward-backward, genetic algorithm and simulated annealing. The models were accepted considering the term selection criterion such as r, q, rse and pred_r. The training and test set were selected using random selection method by selecting randomly 30 % of molecules from data set for test set. Dipole moment and SaaCHE-index descriptors gave negative contribution towards the antiplasmodial activity of 9,10anthraquinones. The coefficient of regression is moderate with weak internal and external predictive power (40 60 %). The descriptors selected did not show clear physical meaning for mechanism of action of anthraquinones. The descriptors selected are mainly structural rather than providing an insight into physico-chemical properties of anthraquinones. The standard errors for all models were relatively high (> 0.9) probably due to human error. This error is probably due the nature of the antiplasmodial assay which requires manual estimation of parasitemia using light microscope. The biological data obtained were not normally distributed which could be due to lack of structural diversity of 9,10-anthraquinones. The presence of outliers in the correlation plots could be due to several factors; the experimental error or the molecules may act as antiplasmodial on a different mechanism of action.

1-Meth­oxy-4-methyl-9,10-anthraquinone

The non-H atoms of the title compound, C16H12O3, lie approximately in a common plane (r.m.s. deviation = 0.032 Å). The methyl C atom is forced away from the carbonyl O atom which can be seen by the widened Cfused ring–Cbenzene–Cmethyl angle of 125.8 (2)°.

2-Formyl-3-hydr­oxy-9,10-anthroquinone

The molecule of the title compound, C15H8O4, is approximately planar. An intramolecular O—H⋯O hydrogen bond is observed between the hydroxy and formyl groups. The crystal used was a nonmerohedral twin, with a minor twin component of 15.9%.