Khoirun Nisa

New cytotoxic phloroglucinols, baeckenones D–F, from the leaves of Indonesian Baeckea frutescens

Three new phloroglucinols, baeckenones D-F (1-3), were obtained from the leaves of Indonesian Baeckea frutescens, along with the known unusual endoperoxide, phloroglucinol (4). The structures of the isolated compounds were elucidated by 1D and 2D NMR and HREIMS spectra. Furthermore, the stereochemistry of baeckenone D (1) was established by an X-ray diffraction analysis. Among the isolated compounds 1-4, baeckenone F (3) showed moderate cytotoxic activities against human pancreatic (PSN-1), lung (A549), and breast (MDA-MB-231) cancer cell lines, with IC50 values of 33.3 μM, 34 μM, and 39.3 μM, respectively.

Two new cyclopentenones and a new furanone from Baeckea frutescens and their cytotoxicities

Two new cyclopentenones, frutescencenones A (1) and B (2), and a new furanone derivative, frutescencenone C (3), together with two known cyclopentenones (4 and 5), were isolated from the leaves of Baeckea frutescens. Their structures were deduced by comprehensive spectroscopic analyses, including 1D and 2D NMR, and HREIMS data. Frutescencenone A (1) showed moderate growth inhibitory activity against human lung A549, pancreatic PSN-1, and breast MDA-MB-231 cancer cell lines, with IC50 values of 36.3μM, 38.2μM, and 29.3μM, respectively. In contrast, frutescencenone C (3) showed selective cytotoxic activity against PSN-1, with an IC50 value of 20.1μM.

Three new abietane-type diterpenoids from the leaves of Indonesian Plectranthus scutellarioides

Three new diterpenoids, spiroscutelones A-C (1-3), along with known diterpene 4, were isolated from the leaves of Plectranthus scutellarioides. Their structures were established based on extensive spectroscopic analyses, including MS and NMR spectroscopy. Spiroscutelone A (1) represents the first example of an abietane-type terpenoid skeleton with a cyclobutane moiety linking the B and C rings. Of compounds 1-4, spiroscutelone B (2) exhibited the most potent cytotoxicities against the three tested human cancer lines [breast (MCF-7), pancreatic (PSN-1), and cervical (HeLa)] with IC50 values ranging from 17.9 μM to 29.8 μM and low cytotoxicity against a lung fibroblast (WI-38) normal cell line.

FORMULATION AND IN VITRO STUDY OF PROPRANOLOL HYDROCHLORIDE CONTROLLED RELEASE FROM CARBOXYMETHYL CHITOSAN-BASED MATRIX TABLETS

Formulation and in vitro study of propranolol hydrochloride controlled release from carboxymethyl chitosanbased matrix tablets have been conducted. Formulations with various concentrations of carboxymethyl chitosan 2% (F1), 4% (F2), 6% (F3) were done by wet granulation method. Compatibility test was conducted by XRD and FTIR spectroscopy to determine interaction between propranolol hydrochloride and polymer excipients. Dissolution profiles was obtained through in vitro tests release using simulated gastric fluid (without enzymes, pH 1.2) for the first 2 h and followed by simulated intestinal fluid (phosphate buffer solution without enzyme, pH 7.2) for 2 h remaining. The dissolution profile of each formulation was fitted with five kinetics modeling of drug release (zero order, first order, Higuchi, Peppas-Korsmeyer, and Hixson-Crowell). The compatibility test results showed that formulation caused physical interactions between propranolol hydrochloride and polymer excipient but doesn’t make crystallinity nature of propranolol hydrochloride disturbed even after formulation. Dissolution profiles of each formulation showed that controlled release of propranolol hydrochloride from the tablet followed Peppas-Korsmeyer model. It is concluded that carboxymethyl chitosan in appropriate proportions is suitable for formulating propranolol hydrochloride controlled release tablets which exhibit Peppas-Korsmeyer release kinetics.

Development and in vitro evaluation of carboxymethyl chitosan based drug delivery system for the controlled release of propranolol hydrochloride

Propranolol hydrochloride is a nonselective β-adrenergic drug and has been used as angina pectoris, antihypertensive, and that of many other cardiovascular disorders. It has a relatively short plasma half-life and duration of action are considered too short in certain circumstances. Thus, its fascinating to elongate the action. The tablet formula was based on extended-release by a propranolol hydrochloride based carboxymethyl chitosan matrix. Here we used direct compression technique with internal wet granulation to prepare the tablets. The tablets were evaluated for physical properties (hardness, weight variation test, friability) and in vitro release studies. There was no interaction observed between propranolol hydrochloride and excipients. Dissolution profiles of each formulation were followed zero order model. In conclusion, these results strongly suggest that in appropriate proportions carboxymethyl chitosan with internal granulation is suitable for formulating propranolol hydrochloride controlled release.

Investigation of Total Phenolic and Flavonoid Contents, and Evaluation of Antimicrobial and Antioxidant Activities from Baeckea frutescens Extracts

Baeckea frutescens L. is a medicinal plant endemic to the tropical area and it has been used by locals for topical and oral ailments. This study investigated total phenolic and flavonoid contents and also evaluated in vitro antimicrobial and antioxidant activities of of Baeckea frutescens crude extracts. These extracts were assessed for their antibacterial activities against strains of Escherichia coli, Staphylococcus aureus, Salmonella thypii, and Pseudomonas aureginosa by the broth micro-dilution methods using a modified tetrazolium-based colorimetric assay (3-(4, 5-dimethylthiazol)-2, 5-diphenyl tetrazolium bromide (MTT) assay). Baeckea frutescens crude extracts were also tested against the stable DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) free-radical. The results indicated that Baeckea frutescens water and ethanol extracts possesed remarkable antibacterial activity with the minimum inhibitory concentration less than 100 μg/ml against Escherichia coli and Salmonella thypi. On the evaluation of the antioxidant activity via DPPH assay, Baeckea frutescens ethanol extracts exhibited a good antioxidant activity with IC50 less than 50 μg/ml and Baeckea frutescens water extracts showed a moderate antioxidant activity with IC50 less than 100 μg/ml.

Filamenting temperature-sensitive mutant Z inhibitors from Glycyrrhiza glabra and their inhibitory mode of action

FtsZ is an essential protein for bacterial cell division, and an attractive and underexploited novel antibacterial target protein. Screening of Indonesian plants revealed the inhibitory activity of the methanol extract of Glycyrrhiza glabra on the Bacillus subtilis FtsZ (BsFtsZ) GTPase, and further bioassay-guided fractionation of the active methanol extract led to the isolation of seven known polyketides (1-7). Among them, gancaonin I (1), glycyrin (3), and isolicoflavanol (5) exhibited anti-BsFtsZ GTPase activities, at levels comparable to that of the synthetic FtsZ inhibitor, Zantrin Z3. Enzymatic assays using a BsFtsZ Val307R mutant protein and in silico simulations suggested that 1, 3, and 5 bind to the cleft on BsFtsZ, as in the case of the previously reported uncompetitive FtsZ inhibitor, PC190723, and thereby display their significant anti-BsFtsZ inhibitory activities. Furthermore, 1 also showed significant inhibitory activity against B. subtilis, with a MIC value of 5μM. The present study provides new insights into the naturally occurring B. subtilis growth inhibitors.