Mohd Azlan Nafiah

Chisomicines A-C, limonoids from Chisocheton ceramicus.

Three new limonoids, chisomicines A-C (1-3), have been isolated from the bark of Chisocheton ceramicus. Their structures were determined by 2D NMR, CD spectroscopic methods, and X-ray analysis. Chisomicine A (1) exhibited NO production inhibitory activity in J774.1 cells stimulated by LPS dose-dependently at high cell viability.

N-Cyanomethylnorboldine: A New Aporphine Isolated from Alseodaphne perakensis (Lauraceae)

A phytochemical study of the bark of Alseodaphne perakensis has yielded three aporphine alkaloids: the new compound N-cyanomethylnorboldine (1), and the two known alkaloids N-methyllaurotetanine (2) and norboldine (3). The isolation was achieved by chromatographic techniques and the structural elucidation was performed via spectral methods, notably 1D- and 2D-NMR, UV, IR, and HRFABMS. The vasorelaxation activity of compound 1 has been studied.

(+)-N-(2-Hydroxypropyl)lindcarpine: A New Cytotoxic Aporphine Isolated from Actinodaphne pruinosa Nees

One new alkaloid; (+)-N-(2-hydroxypropyl)lindcarpine (1), together with four known aporphine alkaloids, (+)-boldine (2) (+)-norboldine (3), (+)-lindcarpine (4) and (+)-methyllindcarpine (5) were isolated from the stem bark of Actinodaphne pruinosa Nees (Lauraceae). (+)-N-(2-Hydroxypropyl)lindcarpine (1) exhibited cytotoxic activity against P-388 murine leukemia cells with an IC50 value of 3.9 μg/mL. Structural elucidation of all the compounds were performed by spectral methods such as 1D- and 2D- NMR, IR, UV, and HRESIMS.

Design, synthesis and cytotoxic evaluation of o-carboxamido stilbene analogues.

Resveratrol, a natural stilbene found in grapes and wines exhibits a wide range of pharmacological properties. Resveratrol is also known as a good chemopreventive agent for inhibiting carcinogenesis processes that target kinases, cyclooxygenases, ribonucleotide reductase and DNA polymerases. A total of 19 analogues with an amide moiety were synthesized and the cytotoxic effects of the analogues on a series of human cancer cell lines are reported. Three compounds 6d, 6i and 6n showed potent cytotoxicity against prostate cancer DU-145 (IC50 = 16.68 μM), colon cancer HT-29 (IC50 = 7.51 μM) and breast cancer MCF-7 (IC50 = 21.24 μM), respectively, which are comparable with vinblastine. The resveratrol analogues were synthesized using the Heck method.

Ultraviolet-visible study on acid-base equilibria of aporphine alkaloids with antiplasmodial and antioxidant activities from Alseodaphne corneri and Dehaasia longipedicellata

The UV-vis spectra of isocorydine 1, norisocorydine 2 and boldine 3 were studied in 2% v/v acetonitrile, at constant ionic strength (0.1 M NaCl, 35 degree Celsius). The pKa values of isocorydine 1 and norisocorydine 2 were 11.75 and 12.07, respectively. Boldine 3 gave a pKa value of 9.16 and 10.44. All of the alkaloids 1–3 were stable at physiological pH; thereby all of them will not ionize, thus permitting the basic nitrogen to be protonated and accumulated within the acidic food vacuole of Plasmodium via pH trapping. Subsequently, acidic food vacuoles that have been neutralized by alkaloids would result in enhancement of the antiplasmodial activity. The alkaloids showed antiplasmodial activity against Plasmodium falciparum and antioxidant activities; DPPH radical scavenging, metal chelating and ferric reducing power. The antioxidant properties of the alkaloids under investigation revealed that in addition to the antiplasmodial activity, the alkaloids can also prevent oxidative damage. It can be prevented by binding free heme and neutralizing the electrons produced during the Plasmodium falciparum mediated haemoglobin destruction in the host. Slightly basic properties of the aforementioned alkaloids, along with their antioxidant activities, are advantageous in improving the suppression of malaria infection that cause less damage to the host.

New Indole Alkaloids from Kopsia Singapurensis (RIDL.)

Study on chemical constituents from Kopsia singapurensis (Apocynaceae) yielded four new aspidofractinines: Singaporentine A (1), N(1)-formylkopsininic acid (2), N(1)-formylkopsininic acid-N(4)-oxide (3), 15-hydroxykopsamine (4); a new aspidospermatan: 14α-hydroxy-N(4)-methylcondylocarpine (5) and a new akuamiline: singaporentinidine (6) together with 18 known indole alkaloids from different parts of the plant. The structures of these compounds were elucidated by combination of various spectroscopic methods.

Antiplasmodial Active Compound from Hernagine Type of Aporphine Alkaloids

Phytochemistry investigation on alkaloids from Alseodaphne pendulifolia Gamb. yielded 3 types of aporphines; Hernagine 1, N-methylhernagine 2, and Oxohernagine 3. Preliminary screening on alkaloids crude extract from this species exhibited an antiplasmodial activity (0.804μg/ml IC50) against Plasmodium falciparum, K1 isolate (resistant strain). Further investigation on isolated compound were found to possess antiplasmodial activity (0.738 1.814μg/ml IC50). This study involves extraction, separation by using various chromatography methods and structural elucidation by spectroscopic technique such as IR, NMR including 1D, 2D-NMR and MS.

Aporphine and Bisbenzylisoquinoline Alkaloids from Roots of AlseodaphneCorneri Kosterm (Lauraceae)

In Malaysia, there about 15 genera and 212 species of Lauraceae family and one of the species that reported contained various aporphine and bisbenzylisoquinoline types alkaloids is Alseodaphne corneri Kosterm. The plant of this family growth in moderate size in Singapore, Malaysia, Jawa, Sumatra and Borneo. The phytochemical study of the roots of Alseodaphne corneri (Lauraceae) had been carried out. Chromatographic separation of the alkaloid extract led to the isolation of four isoquinoline alkaloids namely laetanine (1), boldine (2), O-methyllimacusine (3) and stephasubine (4). The isolation and purification of the alkaloids were achieved using column chromatography (CC) and preparative thin layer chromatography (PTLC). The structural elucidation was performed by spectral methods mainly UV, IR, NMR including 1D-NMR (H and C) and 2D-NMR (COSY, HMQC and HMBC).