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Aspidospermatan-aspidospermatan and eburnane-sarpagine bisindole alkaloids from Leuconotis

Gan CY, Low YY, Robinson WT, Komiyama K, Kam TS

Phytochemistry, 2010 Aug;71(11-12):1365-70.
PMID: 20542302 DOI: 10.1016/j.phytochem.2010.05.015

Leucofoline and leuconoline, representing the first members of the aspidospermatan-aspidospermatan and eburnane-sarpagine subclasses of the bisindole alkaloids, respectively, were isolated from the Malayan Leuconotis griffithii. The structures of these bisindole alkaloids were established using NMR and MS analysis, and in the case of leuconoline, confirmed by X-ray diffraction analysis. Both alkaloids showed weak cytotoxicity towards human KB cells.

Matched MeSH terms: Indole Alkaloids/pharmacology
Biologically active indole alkaloids from Kopsia arborea

Lim KH, Hiraku O, Komiyama K, Koyano T, Hayashi M, Kam TS

J Nat Prod, 2007 Aug;70(8):1302-7.
PMID: 17665953

Nine new indole alkaloids, rhazinoline (1), 19(S)-methoxytubotaiwine (2), 19(R)-methoxytubotaiwine (3), kopsamidine A (4), kopsamidine B (5), kopsinidine A (6), kopsinidine B (7), paucidactine C (8), and pericine N-oxide (9), in addition to several recently reported novel indoles and 34 other known ones, were obtained from the stem-bark extract of the Malayan Kopsia arborea. The structures were determined using NMR and MS analysis. Valparicine (12) showed pronounced cytotoxic effects against KB and Jurkat cells (IC(50) 13.0 and 0.91 microM, respectively).

Matched MeSH terms: Indole Alkaloids/pharmacology*
Alkaloid extracts of Ficus species and palm oil-derived tocotrienols synergistically inhibit proliferation of human cancer cells

Abubakar IB, Lim KH, Loh HS

Nat Prod Res, 2015;29(22):2137-40.
PMID: 25515603 DOI: 10.1080/14786419.2014.991927

Tocotrienols have been reported to possess anticancer effects other than anti-inflammatory and antioxidant activities. This study explored the potential synergism of antiproliferative effects induced by individual alkaloid extracts of Ficus fistulosa, Ficus hispida and Ficus schwarzii combined with δ- and γ-tocotrienols against human brain glioblastoma (U87MG), lung adenocarcinoma (A549) and colorectal adenocarcinoma (HT-29) cells. Cell viability and morphological results demonstrated that extracts containing a mixture of alkaloids from the leaves and bark of F. schwarzii inhibited the proliferation of HT-29 cells, whereas the alkaloid extracts of F. fistulosa inhibited the proliferation of both U87MG and HT-29 cells and showed synergism in combined treatments with either δ- or γ-tocotrienol resulting in 2.2-34.7 fold of reduction in IC50 values of tocotrienols. The observed apoptotic cell characteristics in conjunction with the synergistic antiproliferative effects of Ficus species-derived alkaloids and tocotrienols assuredly warrant future investigations towards the development of a value-added chemotherapeutic regimen against cancers.

Matched MeSH terms: Alkaloids/pharmacology*
Social Functioning of Kratom (Mitragyna speciosa) Users in Malaysia

Singh D, Müller CP, Vicknasingam BK, Mansor SM

J Psychoactive Drugs, 2015 5 8;47(2):125-31.
PMID: 25950592 DOI: 10.1080/02791072.2015.1012610

Kratom (Mitragyna speciosa) is an indigenous plant known for its traditional medicinal use, and for its addiction potential, in Southeast Asia. In recent years, kratom and its major alkaloid, mitragynine, spread worldwide with largely unknown effects on behavior and mental health. Recent studies show that kratom use can lead to dependence and that mitragynine works as an addictive drug in animal studies. Nevertheless, kratom preparations were also suggested as a less harmful substitute in opiate withdrawal. Potential side-effects of prolonged kratom use, however, are currently unclear. The aim of this study was to investigate the social functioning of regular kratom users in Malaysia. A cross-sectional survey was carried out in three northern states of Peninsular Malaysia investigating 293 regular kratom consumers using the Addiction Severity Index in a snowball sampling technique. Findings showed that regular kratom users do not experience major impairments in their social functioning, despite being dependent on kratom for prolonged periods. Our findings suggest that chronic kratom administration does not significantly impair social functioning of users in a natural context in Malaysia.

Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
Fulltext Antidiabetic and antioxidant properties of alkaloids from Catharanthus roseus (L.) G. Don

Tiong SH, Looi CY, Hazni H, Arya A, Paydar M, Wong WF, et al.

Molecules, 2013 Aug 15;18(8):9770-84.
PMID: 23955322 DOI: 10.3390/molecules18089770

Catharanthus roseus (L.) G. Don is a herbal plant traditionally used by local populations in India, South Africa, China and Malaysia to treat diabetes. The present study reports the in vitro antioxidant and antidiabetic activities of the major alkaloids isolated from Catharanthus roseus (L.) G. Don leaves extract. Four alkaloids--vindoline I, vindolidine II, vindolicine III and vindolinine IV--were isolated and identified from the dichloromethane extract (DE) of this plant's leaves. DE and compounds I-III were not cytotoxic towards pancreatic β-TC6 cells at the highest dosage tested (25.0 µg/mL). All four alkaloids induced relatively high glucose uptake in pancreatic β-TC6 or myoblast C2C12 cells, with III showing the highest activity. In addition, compounds II-IV demonstrated good protein tyrosine phosphatase-1B (PTP-1B) inhibition activity, implying their therapeutic potential against type 2 diabetes. III showed the highest antioxidant potential in ORAC and DPPH assays and it also alleviated H₂O₂-induced oxidative damage in β-TC6 cells at 12.5 µg/mL and 25.0 µg/mL.

Matched MeSH terms: Alkaloids/pharmacology
Mitragynine and its potential blocking effects on specific cardiac potassium channels

Tay YL, Teah YF, Chong YM, Jamil MFA, Kollert S, Adenan MI, et al.

Toxicol Appl Pharmacol, 2016 08 15;305:22-39.
PMID: 27260674 DOI: 10.1016/j.taap.2016.05.022

Mitragyna speciosa Korth is known for its euphoric properties and is frequently used for recreational purposes. Several poisoning and fatal cases involving mitragynine have been reported but the underlying causes remain unclear. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. On the other hand, IK1, a Kir current mediated by Kir2.1 channel and IKACh, a receptor-activated Kir current mediated by GIRK channel are also known to be important in maintaining the cardiac function. This study investigated the effects of mitragynine on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells and Xenopus oocytes. The effects on Kir2.1 and GIRK channels currents were also determined in the oocytes. The hERG tail currents following depolarization pulses were inhibited by mitragynine with an IC50 value of 1.62μM and 1.15μM in the transfected cell line and Xenopus oocytes, respectively. The S6 point mutations of Y652A and F656A attenuated the inhibitor effects of mitragynine, indicating that mitragynine interacts with these high affinity drug-binding sites in the hERG channel pore cavity which was consistent with the molecular docking simulation. Interestingly, mitragynine does not affect the hERG expression at the transcriptional level but inhibits the protein expression. Mitragynine is also found to inhibit IKACh current with an IC50 value of 3.32μM but has no significant effects on IK1. Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks.

Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
Physicochemical Characterization of Mitragyna speciosa Alkaloid Extract and Mitragynine using In Vitro High Throughput Assays

Kong WM, Chik Z, Mohamed Z, Alshawsh MA

Comb Chem High Throughput Screen, 2017;20(9):796-803.
PMID: 29076424 DOI: 10.2174/1386207320666171026121820

AIM AND OBJECTIVE: Mitragynine, a major active alkaloid of Mitragyna speciosa, acts as an agonist on µ-opioid receptors, producing effects similar to morphine and other opioids. It has been traditionally utilized to alleviate opiate withdrawal symptoms. Besides consideration about potency and selectivity, a good drug must possess a suitable pharmacokinetic profile, with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-Tox) profile, in order to have a high chance of success in clinical trials.
MATERIAL AND METHOD: The purity of mitragynine in a Mitragyna speciosa alkaloid extract (MSAE) was determined using Ultra-Fast Liquid Chromatography (UFLC). In vitro high throughput ADMETox studies such as aqueous solubility, plasma protein binding, metabolic stability, permeability and cytotoxicity tests were carried out to analyze the physicochemical properties of MSAE and mitragynine. The UFLC quantification revealed that the purity of mitragynine in the MSAE was 40.9%.
RESULTS: MSAE and mitragynine are highly soluble in aqueous solution at pH 4.0 but less soluble at pH 7.4. A parallel artificial membrane permeability assay demonstrated that it is extensively absorbed through the semi-permeable membrane at pH 7.4 but very poorly at pH 4.0. Both are relatively highly bound to plasma proteins (> 85 % bound) and are metabolically stable to liver microsomes (> 84 % remained unchanged). In comparison to MSAE, mitragynine showed higher cytotoxicity against WRL 68, HepG2 and Clone 9 hepatocytes after 72 h treatment.
CONCLUSION: The obtained ADME and cytotoxicity data demonstrated that both MSAE and mitragynine have poor bioavailability and have the potential to be significantly cytotoxic.

Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
Fulltext In Vitro Testing of Potential Entamoeba histolytica Pyruvate Phosphate Dikinase Inhibitors

Saidin S, Othman N, Noordin R

Am J Trop Med Hyg, 2017 Oct;97(4):1204-1213.
PMID: 28820699 DOI: 10.4269/ajtmh.17-0132

Adverse effects and resistance to metronidazole have motivated the search for new antiamoebic agents against Entamoeba histolytica. Control of amoeba growth may be achieved by inhibiting the function of the glycolytic enzyme and pyruvate phosphate dikinase (PPDK). In this study, we screened 10 compounds using an in vitro PPDK enzyme assay. These compounds were selected from a virtual screening of compounds in the National Cancer Institute database. The antiamoebic activity of the selected compounds was also evaluated by determining minimal inhibitory concentrations (MICs) and IC50 values using the nitro-blue tetrazolium reduction assay. Seven of the 10 compounds showed inhibitory activities against the adenosine triphosphate (ATP)/inorganic phosphate binding site of the ATP-grasp domain. Two compounds, NSC349156 (pancratistatin) and NSC228137 (7-ethoxy-4-[4-methylphenyl] sulfonyl-3-oxido-2, 1, 3-benzoxadiazol-3-ium), exhibited inhibitory effects on the growth of E. histolytica trophozoites with MIC values of 25 and 50 μM, and IC50 values of 14 and 20.7 μM, respectively.

Matched MeSH terms: Amaryllidaceae Alkaloids/pharmacology*
Acanthamoebicidal activity of periglaucine A and betulinic acid from Pericampylus glaucus (Lam.) Merr. in vitro

Mahboob T, Azlan AM, Shipton FN, Boonroumkaew P, Nor Azman NS, Sekaran SD, et al.

Exp Parasitol, 2017 Dec;183:160-166.
PMID: 28916456 DOI: 10.1016/j.exppara.2017.09.002

Acanthamoeba species are pathogenic protozoa which account for amoebic keratitis, conjunctivitis and granulomatous amoebic encephalitis. These amoebae form cysts which resist drugs and more effective acanthamoebicidal agents are needed. Medicinal plants could be useful in improving the current treatment strategies for Acanthamoeba infections. In the present study, we examined the amoebicidal effects of Pericampylus glaucus (Lam.) Merr., a medicinal plant used for the treatment of conjunctivitis in Malaysia. Pathogenic Acanthamoeba triangularis were isolated from environmental water samples and treated with different concentrations of fractions obtained from Pericampylus glaucus (Lam.) Merr. as well as main constituents for 24-72 h. Chlorhexidine was used as a reference drug. Ethanol fraction of stem showed significant (p

Matched MeSH terms: Alkaloids/pharmacology*
Curcumin, Piperine, and Capsaicin: A Comparative Study of Spice-Mediated Inhibition of Human Cytochrome P450 Isozyme Activities

Shamsi S, Tran H, Tan RS, Tan ZJ, Lim LY

Drug Metab Dispos, 2017 Jan;45(1):49-55.
PMID: 27821437

Inhibition of cytochrome P450 (P450) enzymes (CYP) has been shown to lower the metabolism of drugs that are P450 substrates and to consequently alter their pharmacokinetic profiles. Curcumin (CUR), piperine (PIP), and capsaicin (CAP) are spice components (SC) that inhibit the activities of a range of P450 enzymes, but the selection of which SC to be prioritized for further development as an adjuvant will depend on the ranking order of the inhibitory potential of the SCs on specific P450 isozymes. We used common human recombinant enzyme platforms to provide a comparative evaluation of the inhibitory activities of CUR, PIP, and CAP on the principal drug-metabolizing P450 enzymes. SC-mediated inhibition of CYP3A4 was found to rank in the order of CAP (IC50 1.84 ± 0.71 µM) ∼ PIP (2.12 ± 0.45 µM) > CUR (11.93 ± 3.49 µM), while CYP2C9 inhibition was in the order of CAP (11.95 ± 4.24 µM) ∼ CUR (14.58 ± 4.57 µM) > PIP (89.62 ± 9.17 µM). CAP and PIP were significantly more potent inhibitors of CYP1A2 (IC50 2.14 ± 0.22 µM and 14.19 ± 4.15 µM, respectively) than CUR (IC50 > 100 µM), while all three SCs exhibited weak activity toward CYP2D6 (IC50 95.42 ± 12.09 µM for CUR, 99.99 ± 5.88 µM for CAP, and 110.40 ± 3.23 µM for PIP). Of the three SCs, CAP thus has the strongest potential for further development into an inhibitor of multiple CYPs for use in the clinic. Data from this study are also useful for managing potential drug-SC interactions.

Matched MeSH terms: Alkaloids/pharmacology*
Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats

Yusoff NHM, Mansor SM, Müller CP, Hassan Z

Behav Brain Res, 2018 06 01;345:65-71.
PMID: 29499286 DOI: 10.1016/j.bbr.2018.02.039

Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABAB receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABAB receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABAB receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABAB receptor.

Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
Phytochemicals and Potential Therapeutic Targets on Toxoplasma gondii Parasite

Abdullahi SA, Unyah NZ, Nordin N, Basir R, Nasir WM, Alapid AA, et al.

Mini Rev Med Chem, 2020;20(9):739-753.
PMID: 31660810 DOI: 10.2174/1389557519666191029105736

Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.

Matched MeSH terms: Alkaloids/pharmacology
Fulltext Efficacy of metabolites of a Streptomyces strain (AS1) to control growth and mycotoxin production by Penicillium verrucosum, Fusarium verticillioides and Aspergillus fumigatus in culture

Danial AM, Medina A, Sulyok M, Magan N

Mycotoxin Res, 2020 May;36(2):225-234.
PMID: 31960351 DOI: 10.1007/s12550-020-00388-7

The objectives of this study were to determine the efficacy of metabolites of a Streptomyces strain AS1 on (a) spore germination, (b) mycelial growth, (c) control of mycotoxins produced by Penicillium verrucosum (ochratoxin A, OTA), Fusarium verticillioides (fumonisins, FUMs) and Aspergillus fumigatus (gliotoxin) and (d) identify the predominant metabolites involved in control. Initial screening showed that the Streptomyces AS1 strain was able to inhibit the mycelial growth of the three species at a distance, due to the release of secondary metabolites. A macroscopic screening system showed that the overall Index of Dominance against all three toxigenic fungi was inhibition at a distance. Subsequent studies showed that the metabolite mixture from the Streptomyces AS1 strain was very effective at inhibiting conidial germination of P. verrucosum, but less so against conidia of A. fumigatus and F. verticillioides. The efficacy was confirmed in studies on a conducive semi-solid YES medium in BioScreen C assays. Using the BioScreen C and the criteria of Time to Detection (TTD) at an OD = 0.1 showed good efficacy against P. verrucosum when treated with the Streptomyces AS1 extract at 0.95 and 0.99 water activity (aw) when compared to the other two species tested, indicating good efficacy. The effective dose for 50% control of growth (ED50) at 0.95 and 0.99 aw were approx. 0.005 ng/ml and 0.15 μg/ml, respectively, with the minimum inhibitory concentration (MIC) at both aw levels requiring > 40 μg/ml. In addition, OTA production was completely inhibited by 2.5 μg/ml AS1 extract at both aw levels in the in vitro assays. Ten metabolites were identified with four of these being predominant in concentrations > 2 μg/g dry weight biomass. These were identified as valinomycin, cyclo(L-Pro-L-Tyr), cyclo(L-Pro-L-Val) and brevianamide F.

Matched MeSH terms: Indole Alkaloids/pharmacology
Cross-reinstatement of mitragynine and morphine place preference in rats

Japarin RA, Yusoff NH, Hassan Z, Müller CP, Harun N

Behav Brain Res, 2021 02 05;399:113021.
PMID: 33227244 DOI: 10.1016/j.bbr.2020.113021

Kratom is a medicinal plant that exhibits promising results as an opiate substitute. However, there is little information regarding the abuse profile of its main psychoactive constituent, mitragynine (MG), particularly in relapse to drug abuse. Using the place conditioning procedure as a model of relapse, this study aims to evaluate the ability of MG to induce conditioned place preference (CPP) reinstatement in rats. To evaluate the cross-reinstatement effects, MG and morphine were injected to rats that previously extinguished a morphine- or MG-induced CPP. Following a CPP acquisition induced by either MG (10 and 30 mg/kg, i.p.) or morphine (10 mg/kg, i.p.), rats were subjected to repeated CPP extinction sessions. A low dose priming injection of MG or morphine produced a reinstatement of the previously extinguished CPP. In the second experiment of this study, a priming injection of morphine (1, 3 and 10 mg/kg, i.p.) dose-dependently reinstated an MG-induced CPP. Likewise, a priming injection of MG (3, 10 and 30 mg/kg, i.p.) was able to dose-dependently reinstate a morphine-induced CPP. The present study demonstrates a cross-reinstatement effect between MG and morphine, thereby suggesting a similar interaction in their rewarding motivational properties. The findings from this study also suggesting that a priming exposure to kratom and an opioid may cause relapse for a previously abused drug.

Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
Fulltext Metabolic Profile of Scytalidium parasiticum-Ganoderma boninense Co-Cultures Revealed the Alkaloids, Flavonoids and Fatty Acids that Contribute to Anti-Ganoderma Activity

Ahmad R, Lim CK, Marzuki NF, Goh YK, Azizan KA, Goh YK, et al.

Molecules, 2020 Dec 16;25(24).
PMID: 33339375 DOI: 10.3390/molecules25245965

In solving the issue of basal stem rot diseases caused by Ganoderma, an investigation of Scytalidium parasiticum as a biological control agent that suppresses Ganoderma infection has gained our interest, as it is more environmentally friendly. Recently, the fungal co-cultivation has emerged as a promising method to discover novel antimicrobial metabolites. In this study, an established technique of co-culturing Scytalidium parasiticum and Ganoderma boninense was applied to produce and induce metabolites that have antifungal activity against G. boninense. The crude extract from the co-culture media was applied to a High Performance Liquid Chromatography (HPLC) preparative column to isolate the bioactive compounds, which were tested against G. boninense. The fractions that showed inhibition against G. boninense were sent for a Liquid Chromatography-Time of Flight-Mass Spectrometry (LC-TOF-MS) analysis to further identify the compounds that were responsible for the microbicidal activity. Interestingly, we found that eudistomin I, naringenin 7-O-beta-D-glucoside and penipanoid A, which were present in different abundances in all the active fractions, except in the control, could be the antimicrobial metabolites. In addition, the abundance of fatty acids, such as oleic acid and stearamide in the active fraction, also enhanced the antimicrobial activity. This comprehensive metabolomics study could be used as the basis for isolating biocontrol compounds to be applied in oil palm fields to combat a Ganoderma infection.

Matched MeSH terms: Alkaloids/pharmacology
Cytotoxic and leishmanicidal aminoglycosteroids and aminosteroids from Holarrhena curtisii

Kam TS, Sim KM, Koyano T, Toyoshima M, Hayashi M, Komiyama K

J Nat Prod, 1998 Nov;61(11):1332-6.
PMID: 9834146

The EtOH extract of the leaves of Holarrhena curtisii yielded five new steroidal alkaloids: 17-epi-holacurtine (3), 17-epi-N-demethylholacurtine (4), holacurtinol (5), 3alpha-amino-14beta-hydroxypregnan-20-one (7), and 15alpha-hydroxyholamine (8), in addition to the known compounds, holacurtine (1), N-demethylholacurtine (2), and holamine (6). All eight compounds showed significant cytotoxic and leishmanicidal activities.

Matched MeSH terms: Alkaloids/pharmacology*
Fulltext Jerantinine A induces tumor-specific cell death through modulation of splicing factor 3b subunit 1 (SF3B1)

Chung FF, Tan PF, Raja VJ, Tan BS, Lim KH, Kam TS, et al.

Sci Rep, 2017 02 15;7:42504.
PMID: 28198434 DOI: 10.1038/srep42504

Precursor mRNA (pre-mRNA) splicing is catalyzed by a large ribonucleoprotein complex known as the spliceosome. Numerous studies have indicated that aberrant splicing patterns or mutations in spliceosome components, including the splicing factor 3b subunit 1 (SF3B1), are associated with hallmark cancer phenotypes. This has led to the identification and development of small molecules with spliceosome-modulating activity as potential anticancer agents. Jerantinine A (JA) is a novel indole alkaloid which displays potent anti-proliferative activities against human cancer cell lines by inhibiting tubulin polymerization and inducing G2/M cell cycle arrest. Using a combined pooled-genome wide shRNA library screen and global proteomic profiling, we showed that JA targets the spliceosome by up-regulating SF3B1 and SF3B3 protein in breast cancer cells. Notably, JA induced significant tumor-specific cell death and a significant increase in unspliced pre-mRNAs. In contrast, depletion of endogenous SF3B1 abrogated the apoptotic effects, but not the G2/M cell cycle arrest induced by JA. Further analyses showed that JA stabilizes endogenous SF3B1 protein in breast cancer cells and induced dissociation of the protein from the nucleosome complex. Together, these results demonstrate that JA exerts its antitumor activity by targeting SF3B1 and SF3B3 in addition to its reported targeting of tubulin polymerization.

Matched MeSH terms: Indole Alkaloids/pharmacology*
Novel Piperine compound AB05 (N-5-(3,4-dimethoxyphenyl) -2E,4E pentadienylpiperidine) inhibits H1N1 influenza virus propagation in vitro

Mohammed A, Velu AB, Al-Hakami AM, Meenakshisundaram B, Esther P, Abdelwahid SA, et al.

Trop Biomed, 2020 Dec 01;37(4):1062-1073.
PMID: 33612758 DOI: 10.47665/tb.37.4.1062

Pandemic H1N1 influenza virus respiratory illness has become an inevitable global health concern. With antigenic drift, it becomes necessary to have drugs over tailor-made HIN1 vaccine every year. In the current study, we screened many Piperine derivative in which, N-5-(3,4-dimethoxyphenyl)-2E,4E-pentadienylpiperidine (AB05) and was further studied for anti-H1N1influenza virus activity and compared with other stains in-vitro on MDCK cell line. Initial cytotoxic doses of AB05 for the MDCK cell line were > 25µM. The results showed a dose-dependent reduction of the viral plaque's in the adsorption assay with EC50 of 0.33 µM. The mechanism of AB05 was by inhibition of matured viral release as evaluated by the time of virus addition with incubation of 6-10 hours. With the promising H1N1 virucidal activity of AB05, we included various strains of human influenza virus to screen AB05 inhibition of Neuraminidase (NA). The result showed 70% NA inhibition in WSN (H1N1), 90% in H3N2 and Influenza B and 49% in Tamiflu resistant H1N1). Further our In silco docking studies substantiated experimental results by showing the difference in binding and cooperation between H1N1 and N3N2. Together these observations illustrate that Piperine derivative AB05 is a promising lead molecule which needs further evaluation in animal models.

Matched MeSH terms: Alkaloids/pharmacology*
Fulltext Potential role of marine species-derived bioactive agents in the management of SARS-CoV-2 infection

Asif M, Saleem M, Yaseen HS, Yehya AH, Saadullah M, Zubair HM, et al.

Future Microbiol, 2021 Nov;16(16):1289-1301.
PMID: 34689597 DOI: 10.2217/fmb-2021-0024

COVID-19, caused by the SARS-CoV-2 outbreak, has resulted in a massive global health crisis. Bioactive molecules extracted or synthesized using starting material obtained from marine species, including griffithsin, plitidepsin and fingolimod are in clinical trials to evaluate their anti-SARS-CoV-2 and anti-HIV efficacies. The current review highlights the anti-SARS-CoV-2 potential of marine-derived phytochemicals explored using in silico, in vitro and in vivo models. The current literature suggests that these molecules have the potential to bind with various key drug targets of SARS-CoV-2. In addition, many of these agents have anti-inflammatory and immunomodulatory potentials and thus could play a role in the attenuation of COVID-19 complications. Overall, these agents may play a role in the management of COVID-19, but further preclinical and clinical studies are still required to establish their role in the mitigation of the current viral pandemic.

Matched MeSH terms: Alkaloids/pharmacology
Fulltext Anti-tumour promoting activity and antioxidant properties of girinimbine isolated from the stem bark of Murraya koenigii S

Kok YY, Mooi LY, Ahmad K, Sukari MA, Mat N, Rahmani M, et al.

Molecules, 2012 Apr 20;17(4):4651-60.
PMID: 22522395 DOI: 10.3390/molecules17044651

Girinimbine, a carbazole alkaloid isolated from the stem bark of Murraya koenigii was tested for the in vitro anti-tumour promoting and antioxidant activities. Anti-tumour promoting activity was determined by assaying the capability of this compound to inhibit the expression of early antigen of Epstein-Barr virus (EA-EBV) in Raji cells that was induced by the tumour promoter, phorbol 12-myristate 13-acetate. The concentration of this compound that gave an inhibition rate at fifty percent was 6.0 µg/mL and was not cytotoxic to the cells. Immunoblotting analysis of the expression of EA-EBV showed that girinimbine was able to suppress restricted early antigen (EA-R). However, diffused early antigen (EA-D) was partially suppressed when used at 32.0 µg/mL. Girinimbine exhibited a very strong antioxidant activity as compared to a-tocopherol and was able to inhibit superoxide generation in the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced differentiated premyelocytic HL-60 cells more than 95%, when treated with the compound at 5.3 and 26.3 µg/mL, respectively. However girinimbine failed to scavenge the stable diphenyl picryl hydrazyl (DPPH)-free radical.

Matched MeSH terms: Alkaloids/pharmacology*

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