Codonopsinine derivatives as potential inhibitory agents against methicillin- resistant staphylococcus aureus (MRSA) / Saiful Azmi Johari

Methicillin-resistant Staphylococcus aureus (MRSA) is a nosocomialrelated and economically-relevant Gram-positive bacterial pathogen that has been known to display multidrug-resistance properties towards a wide range of structurally-unrelated antibiotics and antimicrobial agents. On the other hand, codonopsinine is a plant-based pyrrolidine alkaloid which is known to display remarkable antibiotic, hypotensive and low cytotoxic activity. Previously, 30 codonopsinine derivatives with electron rich functional groups were synthetically produced. In this study, selected microbiological and pre-clinical assays were carried out to investigate the possibility of using codonopsinine derivatives as potential new inhibitory agents against MRSA and methicillin-sensitive S. aureus (MSSA) isolates. In the MIC assay, only two novel compounds, MFM501 and MFM514, showed good inhibitory activity with MIC values between 7.81 to 31.3 μg/ml against 38 MRSA and 13 MSSA isolates. The MBC/MIC ratio exhibited that both active compounds has a bacteriostatic effect against MRSA and MSSA isolates. In the timekill studies, MFM501 showed a time-dependent killing action while MFM514 displayed a concentration-dependent killing effect. MFM514 also exhibited a faster bacteriostatic action than MFM501. Additionally, SEM analysis suggests that both active derivatives may exert its inhibitory activity via bacterial lysis and/or cytoplasmic membrane disruptions which resulted in the various irregular, distorted, shrunken and larger shapes of the treated MRSA cells. In the in vitro cytotoxic assay, both active molecules showed low cytotoxic activity with IC50 value of > 625 μg/ml against three non-cancerous mammalian cells. Following that, oral acute toxicity study revealed that the estimated LD50 value for MFM501 was > 300 mg/kg and 2000 mg/kg and < 5000 mg/kg (Category 5). Finally, in the mouse protection assay, the ED50 values for MFM501 and MFM514 were calculated at 87.16 mg/kg and 29.39 mg/kg dosage, respectively, while both active codonopsinine derivatives exhibited a dose-dependent mice protection trend. This study showed that both active pyrrolidone compounds have the potential to be developed further as clinically active, safe and efficacious anti-MRSA agents. Since the dire need for new antibacterial agents are literally crucial for the survival of mankind, it is hoped that this study will serve as a proof-of concept paper to interested investors and/or healthcare-related companies for further R&D endeavour and/or commercial applications

Efflux Inhibitory Activity Of Selected Phyto-Compounds Against Clinical Isolates Of Multidrug-Resistant Staphylococcus Aureus

Multidrug-resistant Staphylococcus aureus (MRSA) has been reported as one of the main cause of nosocomial infection in the world and ranks as one of the most difficult bacteria to treat in hospitalized patients. Apparently, these multidrug resistance (MDR) traits are caused by an array of MDR efflux pumps in S. aureus. In this study, a panel of identified clinical S. aureus isolates were tested for their multidrug-resistance profile, detection of efflux genes and evaluated against selected phyto-compounds. From the 26 bacterial isolates acquired from two teaching hospitals (HUKM and UMMC) and three ATCC S. aureus reference strains, 19 were confirmed as S. aureus isolates. Out of the 19 isolates, 14 were confirmed as methicillin-resistant S. aureus (MetRSA) via phenotypic and genotypic methods. Fourteen MetRSA isolates exhibit multidrug-resistance against amikacin, erythromycin, gentamicin, norfloxacin, tetracycline and trimethoprim. A methicillin-sensitive S. aureus (MetSSA) with multidrug-resistant trait was also detected. Apart from vancomycin, mupirocin seems to be the most effective antibiotic against all S. aureus isolates. Two MDR efflux genes (mdeA and norA) were detected in all isolates tested. Out of the 19 isolates, 18 harboured the mdeA gene while 16 isolates contained the norA gene. Active efflux activity in S. aureus was detected using modified minimum inhibitory concentration (MIC) assay with ethidium bromide and reserpine as the efflux substrate and efflux inhibitor respectively. From this assay, two MRSA clinical isolates and one ATCC 25923 S. aureus reference strain were selected as test strains against 37 selected phyto-compounds consisting of alkaloids, flavonoids, coumarins and essential oils. Nine compounds namely quinine, harmaline, piperine, cinnamon oil, dicumarol, eriodictyol-7,4’-dimethyl ether, 2’,4-dihydroxy-4’,5’,6’- trimethoxychalcone and naringenin-4’-methyl ether exhibited good efflux inhibitory activity as compared to reserpine. The first two are alkaloids with a methoxyl group at position C6 of an indole and quinolone skeleton, respectively. The last three are flavonoids from different sub-classes of flavanone (eriodictyol-7,4’-dimethyl and ether naringenin-4’-methyl ether) and chalcone (2’,4-dihydroxy-4’,5’,6’-trimethoxychalcone). The similarity observed amongst member of the latter group is the presence of two hydroxyl group attached to their skeletal structures

Pencapaian tahap kemahiran menulis Bahasa Arab sebagai bahasa ketiga dalam kalangan pelajar IPTA / Fauzi Azmi, Saiful Johari Musahar and Prof. Madya Rasid Muhamad

Kajian ini dijalankan dengan tujuan mengenalpasti tahap pencapaian kemahiran menulis dan keberkesanan proses pengajaran dan pembelajaran bahasa Arab sebagai bahasa ketiga atau sebagai subjek elektif di IPTA. Populasi kajian ini terdiri daripada para pelajar yang mengambil subjek bahasa Arab di tahap kedua dan berjumlah 100 orang. Mereka merupakan para pelajar daripada pelbagai fakulti. Kajian ini menggabungkan kaedah kuantitatif dan kualitatif dalam pengumpulan data. Data kuantitatif dan kualitatif yang dikumpul adaJah bertujuan untuk menilai kemahiran menulis para pelajar. dalam kurikulum bahasa Arab di IPTA. Pencapaian kemahiran ini diukur mengikut 11 tahap/peringkat penguasaan kemahiran menulis. Dapatan kajian ini juga memaparkan aspek-aspek kelemahan dan kekuatan serta teknik-teknik pengajaran dan pembelajaran kemahiran menulis

Kemahiran asas menulis perkataan bahasa arab di kalangan pelajar UiTM Pahang / Saiful Johari Musahar, Nur Afiqah Amanina Kamaruzzaman, Roselina Musahar ... [et al.]

Bahasa Arab mempunyai jenis tulisan yang rumit dan unik dalam sistem penulisannya. Untuk mengeja dan menyambung huruf-huruf Arab ini memerlukan pembelajaran secara khusus berkaitan huruf-huruf Arab ini melalui latihan kemahiran menulis. Ini kerana huruf-huruf Arab memiliki bentuk-bentuk karakter penulisan yang berbeza pada setiap huruf dan masih ramai dalam kalangan pelajar yang mengalami kesukaran untuk menulis khususnya dalam menyambung huruf-huruf Arab dari satu huruf kepada huruf lain. Kajian ini adalah bertujuan mengenalpasti kesilapan pelajar dalam asas penulisan bahasa Arab berdasarkan huruf hijaiyah yang boleh disambung sebelumnya dan tidak boleh disambung selepasnya, huruf hijaiyah yang boleh disambung sebelum dan selepas, dan huruf hijaiyah yang terdiri daripada huruf hamzah (ء) secara umumnya tidak boleh disambung dan menyambung dalam satu perkataan. Kajian ini dijalankan dengan menggunakan kaedah soal selidik. Oleh itu, diharapkan kajian ini dapat membantu pelajar memahami tentang asas penulisan bahasa Arab dalam kemahiran menulis

Inhibitory and resistance-modifying potential of plant-based alkaloids against methicillin-resistant staphylococcus aureus (MRSA)

Increased prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has become a major threat to the health sector worldwide due to their virulence, limited therapeutic options and their distribution in both hospital and community settings. Discovery and development of new anti-MRSA agents as alternatives to the very few antibiotics left in the armamentarium are, thus, urgently required. Recently, an efflux mechanism in MRSA has been identified as one of the main contributors of resistance towards various structurally unrelated antibiotics. The potential of reserpine (a phytoalkaloid) as efflux pump inhibitor (EPI) against various microbes remains limited as the concentration needed for inhibition is toxic to humans. This study therefore aimed to evaluate 13 alkaloid compounds as potential inhibitory agents and/or potential EPIs against a panel of three MRSA isolates which not only differ in their susceptibility to vancomycin (amongst the last drugs available to treat serious MRSA infection), but also exhibited active efflux activity. Results indicated berberine's moderate inhibitiory activity against two MRSA isolates scoring a minimum inhibitory concentration (MIC) value of 125 microg/ml. Notable efflux inhibitory activity (ranging from two- to eightfold Ethidium Bromide MIC reduction) meanwhile was detected from quinine, piperine and harmaline using reserpine as the positive control. Findings from this study support the opinion that a vast number of potential phytocompounds with pharmacological potential await discovery. Therapeutic application of these compounds, however, warrants further investigation to ascertain their pharmacodynamics and safety aspects

Chemical compositions and antimicrobial activity of twig essential oils from three Xylopia (Annonaceae) species

The chemical composition of twig essential oils of Xylopia malayana, Xylopia elliptica and Xylopia fusca were analyzed using GC and GCMS. Both X. malayana (12.9%) and X. fusca (11.8%) twig oils contained spathulenol as the major constituent while X. elliptica twig oil was found to be rich in terpinen-4-ol (11.9%). The antimicrobial activities of the essential oils were evaluated against six gram positive bacteria, two gram negative bacteria and yeast by using the broth microdilution method. The twig oil of X. elliptica at a concentration ranging from 156 to 625 μg/ml was found to be active against all bacterial and yeast strains tested. Both X. malayana and X. fusca twig oils demonstrated weak activity toward all microorganisms tested with the MIC value of 5000 μg/ml. Gram negative bacteria’s, Pseudomonas aeruginosa and Escherichia coli seemed to be resistant to the essential oils tested. α-Pinene showed moderate to strong inhibitory effect against all the microorganism strains tested with the MIC value ranging from 325 to 2500 μg/ml, as compared to the other standard compounds which showed weak inhibitory even at the highest concentrations used. This finding demonstrated that the twig oil of X.elliptica possesses antimicrobial activity which may be useful and potential ingredient in the production of health care products.Key words: Xylopia twigs, essential oils, GC &amp; GCMS analysis, antimicrobial activity

New Access to Pyrano[2,3-<i>c</i>]pyrazole-3-carboxylates via Domino Four-Component Reaction and Their Antimicrobial Activity

A library of some novel classes of pyrano[2,3-c]pyrazole-3-carboxylates was synthesized by employing uncatalyzed domino four-component reaction using diethyloxaloacetate, hydrazine hydrate, aldehydes and malononitrile in refluxing of ethanol-acetic acid solvent systems. Series of domino reactions involving of pyrazolone formation, Michael addition, and Thorpe-Ziegler cyclization reaction managed to produce the cyclized products from moderate to excellent yield. This protocol provides a reliable, general and salient procedure for the title compound using a one-pot approach. Preliminary biological screening unveiled limited potentials of this class of compounds for antimicrobial lead compound due to its limited solubility properties

Kajian kontrastif terhadap persamaan implikatur ayat perintah dalam bahasa Arab dan bahasa Melayu

Sumbangan kajian linguistik kontrastif sangat besar dan penting dalam pengajaran bahasa asing. Kajian kontrastif ialah mengintegrasikan antara dua atau lebih bahasa yang berlainan rumpun. Fokus kajian ialah kepada aspek persamaan dan perbezaan antara bahasa-bahasa tersebut. .Kajian linguistik kontrastif diperkenalkan kepada para pelajar yang mempelajari bahasa asing bagi tujuan hasil pembelajaran yang lebih efektif, efesien, mudah dan menarik. Kajian ini menyentuh salah satu topik kontras antara bahasa Arab (BA) dan bahasa Melayu (BM), iaitu persamaan implikatur ayat perintah. Implikatur ialah suatu bentuk pentafsiran makna yang melangkaui makna tersurat dalam sesebuah ayat. Objektif kajian ini untuk mengenalpasti persamaan implikatur gaya bahasa perintah dalam kedua-dua bahasa ini. Kajian ini merupakan kajian kualitatif dan analisis kontras berdasarkan teks dalam kedua-dua bahasa. Teori transformasi generatif (TG) dan teori pragmatik diaplikasi dalam menganalisis persamaan ini. Dapatan kajian menjelaskan terdapat 28 makna implisit yang sama dalam bahasa Arab (BA) dan bahasa Melayu (BM). Kajian ini menyumbang kepada suatu penerokaan baharu dalam kajian linguistik bahasa Arab (BA) dan bahasa Melayu (BM). Hasil kajian ini juga boleh membantu para pengajar bahasa asing untuk memahami dan mendalami titik persamaan serta membina kurikulum baharu bagi tujuan mempersembahkan bahan pengajaran yang lebih mudah dan menarik. Para pelajar bahasa asing juga dapat menguasai bahan pengajaran tersebut dengan cepat dan menyeronokkan

Efflux genes and active efflux activity detection in of methicillin-resistant Staphylococcus aureus (MRSA).

Efflux-mediated resistance has been recognized as an important contributor of antibiotic resistance in bacteria, especially in methicillin-resistant Staphylococcus aureus (MRSA) isolates. This study was carried out to detect and analyze efflux genes (norA and mdeA) and active efflux activity in a collection of Malaysian MRSA and methicillin-sensitive S. aureus (MSSA) clinical isolates. Nineteen isolates including three ATCC S. aureus reference strains were subjected to PCR detection and DNA sequence analysis for norA and mdeA and active efflux detection using modified minimum inhibitory concentration (MIC) assay. From the 19 isolates, 18 isolates harboured the mdeA gene while 16 isolates contained norA gene. DNA sequence analysis reveals 98–100% correlation between the PCR product and the published DNA sequences in GenBank. In addition, 16 isolates exhibited active efflux activity using the ethidium bromide (EtBr)- reserpine combination MIC assay. To our knowledge, this is the first report on the detection of efflux genes and active efflux activity amongst Malaysian clinical isolates of MRSA/MSSA. Detection of active efflux activity may explain the previous report on efflux-mediated drug resistance profile amongst the local clinical isolates

Cytotoxic Activity of MFM 501, a Novel Codonopsinine Derivative, against Methicillin-Resistant Staphylococcus aureus Clinical Isolates

28 new pyrrolidine types of compounds as analogues for natural polyhydroxy alkaloids of codonopsinine were evaluated for their anti-MRSA activity using MIC and MBC value determination assay against a panel of S. aureus isolates. One pyrrolidine compound, MFM 501, exhibited good inhibitory activity with MIC value of 15.6 to 31.3 g/mL against 55 S. aureus isolates (43 MRSA and 12 MSSA isolates). The active compound also displayed MBC values between 250 and 500 g/mL against 58 S. aureus isolates (45 MRSA and 13 MSSA isolates) implying that MFM 501 has a bacteriostatic rather than bactericidal effect against both MRSA and MSSA isolates. In addition, MFM 501 showed no apparent cytotoxicity activity towards three normal cell lines (WRL-68, Vero, and 3T3) with IC 50 values of &gt;625 g/mL. Selectivity index (SI) of MFM 501 gave a value of &gt;10 suggesting that MFM 501 is significant and suitable for further in vivo investigations. These results suggested that synthetically derived intermediate compounds based on natural products may play an important role in the discovery of new anti-infective agents against MRSA