Pusat Penyelidikan Dadah dan Ubat-Ubatan - Tesis

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Studies On The Chemistry, Anticholinesterase Activity And Toxicity Of Mitragyna Speciosa (Kratom) Alkaloids
(2024-06)
Chear, Nelson Jeng Yeou
Mitragyna speciosa (korth) havil. Is a medicinal plant native to malaysia, traditionally used to treat pain, diabetes, hypertension, and drug addiction. It is also consumed as a tonic beverage to enhance alertness, attention and working performance among labourers and farmers. Most pharmacological activities documented for m. Speciosa focus on opioid-related activities. Research on the potential therapeutic effects of m. Speciosa on the cholinergic neurotransmission system is still scarce. Only one study has reported the anticholinesterase activity of the methanol extract and mitragynine prepared from thai m. Speciosa. Therefore, this study aims to identify potential cholinesterase inhibitors from m. Speciosa using a bioassay-guided isolation approach. A total of thirteen alkaloids were isolated and characterized from the alkaloid extract using modern chromatographic techniques and spectroscopic methods. The isolated alkaloids were mitragynine (87), speciociliatine (88), speciogynine (89), mitraciliatine (90), paynantheine (91), corynantheidine (101), corynoxine (81), corynoxine b (82), mitrafoline (125), mitragynine oxindole b (117), mitragynine oxindole a (116), 17(z)-speciociliatine (146), and speciociliatine n-oxide (98). Two of these alkaloids, 17(z)-speciociliatine (146) and speciociliatine n-oxide (98), are the new compounds from m. Speciosa. Notably, 17(z)-speciociliatine (146) is the fourth isomer of mitragynine (87), in addition to (88), (89) and (90).
Cross-reinstatement Models Of Mitragynine-morphine Drugseeking Addictive Behaviour And Dopaminergic Involvement In Sprague-dawley Rats
(2024-09)
Japarin, Rima Atria
Kratom (Mitragyna speciosa Korth.) is a medicinal herb which gained fame for its potential as an opioid substitute. Nevertheless, little is known about the abuse potential of its major alkaloid, mitragynine, especially in relapse to drug abuse. Therefore, the extinction-reinstatement models including the conditioned place preference (CPP) and intravenous self-administration (IVSA) paradigms, were employed to model the relapse mechanism in Sprague-Dawley rats. In the first part of the study, mitragynine administered non-contingently in morphine-addicted rats following extinction was investigated. Following CPP acquisition induced by either mitragynine (30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated mitragynine-induced CPP. Similarly, a priming injection of mitragynine (3, 10 and 30 mg/kg, i.p.) dose-dependently reinstated morphine-induced CPP. In the IVSA study, rats were initially trained to intravenously self-administer morphine (0.5 mg/kg/infusion) under a fixed ratio-3 schedule of reinforcement. Removal of both morphine infusions and drug-associated cues led to the extinction of drug-seeking behaviour. Reinstatement tests were made following a randomised order of mitragynine (3, 10 and 30 mg/kg), morphine (5 mg/kg) and vehicle injections. Mitragynine priming at 10 mg/kg resulted in the reinstatement of morphine-seeking behaviour but higher mitragynine dose (30 mg/kg) suppressed the seeking response. In order to understand the mechanism underlying the rewarding properties of mitragynine in relapse, the involvement of dopaminergic system in the acquisition, expression and reinstatement phase was studied. Therefore, the second part of the study was conducted using a selective dopamine (DA) D1 receptor antagonist, SCH-23390. For acquisition, rats were pre-treated with SCH- 23390 (0, 0.1 and 0.3 mg/kg, i.p.) prior to mitragynine (10 mg/kg) conditioning sessions. Next, the effects of DA D1 receptor antagonist were tested on the expression of mitragynine-induced CPP. Subsequently, the effects of a mitragyninepriming dose (5 mg/kg) on the reinstatement of extinguished CPP were tested. The results showed that SCH-23390 dose-dependently suppressed the acquisition of mitragynine-induced CPP but no effect on the expression of mitragynine-induced CPP. Additionally, blockade of the D1-like receptor during conditioning did not prevent mitragynine priming effects in CPP reinstatement test, implying no role of the DA D1 receptor in reinstatement sensitivity. Altogether, these findings suggest that exposure to mitragynine may increase the likelihood of relapsing to opioids, suggesting that mitragynine’s potential as an opioid management treatment merits further scientific assessment of its ability to trigger relapse to opioid abuse.
Chemical Constituents And Cytotoxocity Of The Stem Bark Calophyllum Lanigerum Var. Austrocoriaceum (Whitemore) P. F. Stevens And Calophyllum Andersonii P. F. Stevens
(2024-04)
Mokhtar, Norisha
Plants from the genus Calophyllum, have gained the interest of phytochemists due to the exciting new discoveries of its bioactive constituents. Phytoconstituents such as coumarins, chromanones, xanthones, and triterpenoids are frequently discovered phytochemical groups in this genus. These phytochemicals proven to possess potential pharmacological importance that are essential for scientists to subject it in pharmacotherapeutic applications in treating targeted diseases. For example, used for pharmacotherapeutic purpose in treating HIV, cancer, and inflammatory related diseases. In this study, the stem bark of Calophyllum lanigerum and Calophyllum andersonii were investigated by extracting, isolating, and characterising the possible phytochemicals that present and assessing their cytotoxic activity, respectively. Five phenolics and two triterpenoids have been isolated from the stem bark of C. lanigerum. The phenolic compounds were identified as caloteysmannic acid (A), isocalolongic acid (B), calolongic acid (C), euxanthone (D), calanone (E), and two common triterpenoids, friedelin (F) and stigmasterol (G). Meanwhile, calanone (E) and its constitutional isomer, isocalanone (H) together with soulattrolide (I) and friedelin (F) were isolated from the stem bark of C. andersonii. Chromanone acids (Compounds A and B) were reported for the first time in C. lanigerum in Sarawak region. The chemical structures of these isolated compounds were elucidated using detailed spectroscopic techniques including NMR (1D, 2D), MS, UV-Vis, FTIR. Extracts (n- xxi hexane, chloroform, ethyl acetate) and compounds (A, B, E, and H) from both Calophyllum species were subjected for their cytotoxicity against HeLa Chang liver (human cervix carcinoma) and HL-7702 (human normal liver) cell lines. Only ethyl acetate extract from C. lanigerum exhibited promising cytotoxicity, with IC50 value of 34.13 ± 3.82 μg/mL, while n-hexane and chloroform extracts showed moderate cytotoxicity against Hela Chang liver cell line [IC50: 93.84 ± 9.35 μg/mL and 81.33 ± 2.41 μg/mL, respectively]. The observed cytotoxic effects of the ethyl acetate extract suggest its potential for further development as an anticancer agent.
Phytochemical Studies And Cytotoxicity Assessment Of Stem Bark Extracts From Calophyllum Macrocarpum Hook. F. And Calophyllum Recurvatum P. F. Stevens
(2024-04)
Firouz, Noor Syarafana
Numerous Calophyllum sp. have long been valued widely in Asian traditional medicine especially in Malaysia. The modern natural product-based research on the genus Calophyllum has further revealed a variety of biological functions exhibited by these plants, such as inhibition of HIV, antioxidant, and cytotoxicity. Species from the genus Calophyllum are also abundant in phenolic compounds especially xanthones and coumarins. However, Calophyllum macrocarpum and Calophyllum recurvatum are among the species that still need more scientific documentation on the phytochemistry and pharmacological aspects. In this research project, the stem bark of Calophyllum macrocarpum and Calophyllum recurvatum were being subjected for phytochemical investigation, which led to the isolation of various phytochemicals such as xanthones and coumarins. Extensive chromatographic separations and purifications on the stem bark of C. macrocarpum (n-hexane and chloroform extracts) resulted in isolation of prenylated xanthones; ananixanthone (1), trapezifolixanthone (2), 8-deoxygartanin (3), as well as triterpenoid; stigmasterol (4) and friedelin (5). Furthermore, thwaitesixanthone (6), teysmanone A (7), soulattrolide (8), calanone (9), as well as friedelin (5) were successfully being isolated from the stem bark of C. recurvatum (n-hexane and chloroform extracts).
Phytochemistry Of Calophyllum Havilandii P.F. Stevens And Calophyllum Lowei Planch. & Triana And Their Biological Activities
(2024-07)
Zailan, Ahmad Alif Danial
Plants from the genus Calophyllum (Calophyllaceae) is a treasure trove of various interesting phytochemicals with impressive structural diversity. These phytochemical constituents were often discovered as derivatives in the classes of phenolics, such as xanthones, coumarins, chromanones, phloroglucinols, and flavonoids. Many of them are proven to exhibit wide range of pharmacological as well as biological activities, such as cytotoxic, anti-viral, anti-inflammatory, and anti-microbial. In this study, the process of extraction, isolation, and characterization of phytochemicals were conducted on the stem bark of two endemic Malaysian Calophyllum species from Sarawak, namely Calophyllum havilandii and Calophyllum lowei. All of the isolated phytochemicals were characterized and elucidated using extensive spectroscopic techniques such as MS, IR, UV, and NMR.

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