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  1. Tobacco and the Commonwealth: a call to action
    Krishnan P, Mungherera M, Jones SB
    Lancet, 2003 May 17;361(9370):1669-70.
    PMID: 12767730 DOI: 10.1016/S0140-6736(03)13381-8
  2. Fulltext Survey on health status of heavy vehicle drivers in Klang valley
    Krishnan P, Hashim N, Rani U, Lung JK
    Med J Malaysia, 1998 Dec;53(4):449-51.
    PMID: 10971995
    A survey was carried out using a medical examination format that was prepared by the Malaysian Medical Association. The findings of the survey show that of the 266 cases surveyed, 64 drivers (24% of cases surveyed) are either totally unfit to drive or temporarily unfit to drive heavy goods and passenger vehicles. This is clear indication that the current format that is being used by the Road Transport Department is inadequate and needs to be reviewed. It must also be stressed that all the above 64 drivers have been certified fit using the existing Road Transport Department format and are currently driving in our highways and roads. Heavy vehicle goods and passenger vehicle drivers if not properly examined and medically certified are not only be endangering their own lives but also that of others. It is therefore recommended that based on the data available from this survey, the Road Transport Department should seriously consider adopting the medical examination format that was formalised by the Malaysian Medical Association and used in this survey.
  3. A comprehensive review on the chemical constituents, sesquiterpenoid biosynthesis and biological activities of Sarcandra glabra
    Chu JN, Krishnan P, Lim KH
    Nat Prod Bioprospect, 2023 Nov 27;13(1):53.
    PMID: 38010490 DOI: 10.1007/s13659-023-00418-8
    Sarcandra glabra (Thunb.) Nakai is a perennial evergreen herb categorised within the Sarcandra Gardner genus under the Chloranthaceae family. Indigenous to tropical and subtropical regions of East Asia and India, this species is extensively distributed across China, particularly in the southern regions (Sichuan, Yunnan, and Jiangxi). In addition to its high ornamental value, S. glabra has a rich history of use in traditional Chinese medicine, evident through its empirical prescriptions for various ailments like pneumonia, dysentery, fractures, bruises, numbness, amenorrhea, rheumatism, and other diseases. Besides, modern pharmacological studies have revealed various biological activities, such as antitumour, anti-bacterial, anti-viral anti-inflammatory and immunomodulatory effects. The diverse chemical constituents of S. glabra have fascinated natural product researchers since the 1900s. To date, over 400 compounds including terpenoids, coumarins, lignans, flavonoids, sterols, anthraquinones, organic acids, and organic esters have been isolated and characterised, some featuring unprecedented structures. This review comprehensively examines the current understanding of S. glabra's phytochemistry and pharmacology, with emphasis on the chemistry and biosynthesis of its unique chemotaxonomic marker, the lindenane-type sesquiterpenoids.
  4. Fulltext Knowledge of COVID-19 and Awareness of Physiotherapy Rehabilitation among Clinical Physiotherapy Students: A Cross-Sectional Study
    Krishnan P, Krishnan K, Chan WK
    Malays J Med Sci, 2022 Dec;29(6):115-122.
    PMID: 36818893 DOI: 10.21315/mjms2022.29.6.11
    BACKGROUND: Physiotherapy rehabilitation improves patients' activity in daily life and helps them return to work. Physiotherapy rehabilitation for COVID-19 patients mainly focuses on respiratory and functional rehabilitation assessment. This research project aims to assess the knowledge of COVID-19 and awareness of physiotherapy rehabilitation for COVID-19 patients among clinical physiotherapy students and the relationship between these variables.

    METHODS: A preliminary, cross-sectional study was conducted on 159 clinical physiotherapy students from various education backgrounds. A three-part questionnaire assessing socio-demographic variables, knowledge of COVID-19 and awareness of physiotherapy rehabilitation for COVID-19 patients was distributed among clinical students from major physiotherapy programmes at tertiary institutions. Descriptive statistics, Chi-square tests and Spearman correlation tests were used for data analysis.

    RESULTS: Most of the respondents (95.6%) were categorised as having an above average knowledge on COVID-19. Eighty-seven respondents (54.7%) were categorised as having an above average awareness of physiotherapy rehabilitation for COVID-19 patients. The knowledge of COVID-19 was positively correlated with awareness of physiotherapy rehabilitation (P < 0.05).

    CONCLUSION: This research study showed that the knowledge of COVID-19 and awareness level of physiotherapy rehabilitation in COVID-19 patients was above average among clinical physiotherapy students. The association between knowledge of COVID-19 and awareness of physiotherapy rehabilitation among clinical physiotherapy students had a weak positive correlation.

  5. Concise synthesis of the vasorelaxant alkaloids schwarzinicines A and B
    Lee FK, Krishnan P, Muhamad A, Low YY, Kam TS, Ting KN, et al.
    Nat Prod Res, 2021 Mar 22.
    PMID: 33749454 DOI: 10.1080/14786419.2021.1903005
    A concise synthesis of the 1,4-diarylbutanoid-phenethylamine alkaloids, schwarzinicines A (1) and B (2), recently isolated from Ficus schwarzii, is reported. Key steps include a Claisen condensation to assemble the 1,4-diaryl-2-butanone intermediate, followed by a reductive amination to furnish the core skeleton of the target compounds. The overall synthetic yields of 1 and 2 were 9.1% and 3.5%, respectively. Synthetic (-)-1, (+)-1 and (±)-1 exhibited comparable vasorelaxation as natural schwarzinicine A on rat isolated aortic rings, suggesting that the observed vasorelaxant effects were not influenced by the chirality at C-2.
  6. Human leukocyte antigen (HLA) class II association in chronic hepatitis B patients with hepatocellular carcinoma in a Malay population: A pilot study
    Krishnan PB, Abdullah M, Hudu SA, Sekawi Z, Tan SS, Amin-Nordin S
    Trop Biomed, 2019 Sep 01;36(3):703-708.
    PMID: 33597492
    Asian countries account for almost three quarter of hepatocellular carcinoma (HCC) reported globally and chronic hepatitis B infection is one of the main contributors. Clinical observations show that Malay patients with chronic hepatitis B and HCC tend to have a worse outcome, when compared to other two major races in Malaysia. The objectives of this study was to determine the frequency of human leukocyte antigen (HLA) class II alleles in chronic hepatitis B patients with HCC among Malays compared to the general population to identify potential associations of HLA alleles with this disease. HLA class II typing was performed in chronic hepatitis B patients with hepatocellular carcinoma (n=12) by -polymerase chain reaction, sequence specific primer (PCR-SSP) method. There were higher allelic frequencies of certain HLA-DQB1 and HLA-DRB1 alleles; HLA-DQB1*03 (07) (41.7%), and HLA-DRB1*12 (41.7% vs 28.6%) and compared to controls (41.7% vs 29.7%). However, there was no significant statistical correlation found when compared with the normal healthy general population. This study provides an insight into the HLA Class II association with chronic hepatitis B and hepatocellular carcinoma in Malays. However, findings from this study should be validated with a larger number of samples using a high resolution HLA typing.
  7. Unusual phenethylamine-containing alkaloids from Elaeocarpus tectorius
    Ezeoke MC, Krishnan P, Sim DS, Lim SH, Low YY, Chong KW, et al.
    Phytochemistry, 2018 Feb;146:75-81.
    PMID: 29247894 DOI: 10.1016/j.phytochem.2017.12.003
    From the leaves of Elaeocarpus tectorius (Lour.) Poir. four previously undescribed phenethylamine-containing alkaloids were isolated, namely, tectoricine, possessing an unprecedented isoquinuclidinone ring system incorporating a phenethylamine moiety, tectoraline, representing a rare alkamide incorporating two phenethylamine moieties, and tectoramidines A and B, representing the first naturally occurring trimeric and dimeric phenethylamine alkaloids incorporating an amidine function. The structures of these alkaloids were established by detailed spectroscopic analysis. The absolute configuration of tectoricine was determined by comparison of the experimental and calculated ECD spectra. Plausible biosynthetic pathways to the four alkaloids are proposed.
  8. Alstoscholactine and Alstolaxepine, Monoterpenoid Indole Alkaloids with γ-Lactone-Bridged Cycloheptane and Oxepane Moieties from Alstonia scholaris
    Krishnan P, Lee FK, Chong KW, Mai CW, Muhamad A, Lim SH, et al.
    Org. Lett., 2018 12 21;20(24):8014-8018.
    PMID: 30543301 DOI: 10.1021/acs.orglett.8b03592
    Two new monoterpenoid indole alkaloids, alstoscholactine (1) and alstolaxepine (2), were isolated from Alstonia scholaris. Compound 1 represents a rearranged stemmadenine alkaloid with an unprecedented C-6-C-19 connectivity, whereas compound 2 represents a 6,7- seco-angustilobine B-type alkaloid incorporating a rare γ-lactone-bridged oxepane ring system. Their structures and absolute configurations were determined by spectroscopic analyses. Compound 1 was successfully semisynthesized from 19 E-vallesamine. Compound 2 induced marked vasorelaxation in rat isolated aortic rings precontracted with phenylephrine.
  9. Schwarzinicines A-G, 1,4-Diarylbutanoid-Phenethylamine Conjugates from the Leaves of Ficus schwarzii
    Krishnan P, Lee FK, Yap VA, Low YY, Kam TS, Yong KT, et al.
    J Nat Prod, 2020 01 24;83(1):152-158.
    PMID: 31935094 DOI: 10.1021/acs.jnatprod.9b01160
    Schwarzinicines A-G (1-7), representing the first examples of 1,4-diarylbutanoid-phenethylamine conjugates, were isolated from the leaves of Ficus schwarzii. The structures of these compounds were determined by detailed analysis of their MS, 1D and 2D NMR data. Compounds 1-4 exhibited pronounced vasorelaxant effects in the rat isolated aorta (Emax 106-120%; EC50 0.96-2.10 μM). However, compounds 1 and 2 showed no cytotoxic effects against A549, MCF-7, and HCT 116 human cancer cells (IC50 > 10 μM).
  10. Pentacyclic and hexacyclic cucurbitacins from Elaeocarpuspetiolatus
    Cho ES, Krishnan P, Loh HS, Daly JM, Leong CO, Mai CW, et al.
    Phytochemistry, 2021 Oct 27;193:112988.
    PMID: 34717280 DOI: 10.1016/j.phytochem.2021.112988
    Four undescribed cucurbitacins, designated as petiolaticins A-D, and four known cucurbitacins were isolated from the bark and leaves of Elaeocarpus petiolatus (Jack) Wall. Their chemical structures were elucidated based on detailed analyses of the NMR and MS data. The absolute configuration of petiolaticin A was also determined by X-ray diffraction analysis. Petiolaticin A represents a cucurbitacin derivative incorporating a 3,4-epoxyfuranyl-bearing side chain, while petiolaticin B possesses a furopyranyl unit fused to the tetracyclic cucurbitane core structure. Petiolaticins A, B, and D were evaluated in vitro against a panel of human breast, pancreatic, and colorectal cancer cell lines. Petiolaticin A exhibited the greatest cytotoxicity against the MDA-MB-468, MDA-MB-231, MCF-7, and SW48 cell lines (IC50 7.4, 9.2, 9.3, and 4.6 μM, respectively). Additionally, petiolaticin D, 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one, and 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one 3-O-β-D-glucopyranoside were tested for their ability to inhibit cell entry of a pseudotyped virus bearing the hemagglutinin envelope protein of a highly pathogenic avian influenza virus. Petiolaticin D showed the highest inhibition (44.3%), followed by 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one (21.0%), and 16α,23α-epoxy-3β,20β-dihydroxy-10αH,23βH-cucurbit-5,24-dien-11-one 3-O-β-D-glucopyranoside showed limited inhibition (9.0%). These preliminary biological assays have demonstrated that petiolaticins A and D possess anticancer and antiviral properties, respectively, which warrant for further investigations.
  11. A Bis-benzopyrroloisoquinoline Alkaloid Incorporating a Cyclobutane Core and a Chlorophenanthroindolizidine Alkaloid with Cytotoxic Activity from Ficus fistulosa var. tengerensis
    Al-Khdhairawi AAQ, Krishnan P, Mai CW, Chung FF, Leong CO, Yong KT, et al.
    J Nat Prod, 2017 10 27;80(10):2734-2740.
    PMID: 28926237 DOI: 10.1021/acs.jnatprod.7b00500
    Tengerensine (1), isolated as a racemate and constituted from a pair of bis-benzopyrroloisoquinoline enantiomers, and tengechlorenine (2), purified as a scalemic mixture and constituted from a pair of chlorinated phenanthroindolizidine enantiomers, were isolated from the leaves of Ficus fistulosa var. tengerensis, along with three other known alkaloids. The structures of 1 and 2 were determined by spectroscopic data interpretation and X-ray diffraction analysis. The enantiomers of 1 were separated by chiral-phase HPLC, and the absolute configurations of (+)-1 and (-)-1 were established via experimental and calculated ECD data. Compound 1 is notable in being a rare unsymmetrical cyclobutane adduct and is the first example of a dimeric benzopyrroloisoquinoline alkaloid, while compound 2 represents the first naturally occurring halogenated phenanthroindolizidine alkaloid. Compound (+)-1 displayed a selective in vitro cytotoxic effect against MDA-MB-468 cells (IC50 7.4 μM), while compound 2 showed pronounced in vitro cytotoxic activity against all three breast cancer cell lines tested (MDA-MB-468, MDA-MB-231, and MCF7; IC50 values of 0.038-0.91 μM).
  12. Quinoline, Indole, and Isogranatanine Alkaloids from Malayan Leuconotis eugeniifolia
    Tan YS, Ng MP, Tan CH, Tang WK, Sim KS, Yong KT, et al.
    J Nat Prod, 2024 Feb 23;87(2):286-296.
    PMID: 38284153 DOI: 10.1021/acs.jnatprod.3c00960
    Nine new alkaloids, eugeniinalines A-H (1-8) and (+)-eburnamenine N-oxide (9), comprising one quinoline, six indole, and two isogranatanine alkaloids, were isolated from the stem-bark extract of the Malayan Leuconotis eugeniifolia. The structures and absolute configurations of these alkaloids were established based on the analysis of the spectroscopic data, GIAO NMR calculations, DP4+ probability analysis, TDDFT-ECD method, and X-ray diffraction analysis. Eugeniinaline A (1) represents a new pentacyclic quinoline alkaloid with a 6/6/5/6/7 ring system. Eugeniinaline G (7) and its seco-derivative, eugeniinaline H (8), were the first isogranatanine alkaloids isolated as natural products. The known alkaloids leucolusine (10) and melokhanine A (11) were found to be the same compound, based on comparison of the spectroscopic data of both compounds, with the absolute configuration of (7R, 20R, 21S). Eugeniinalines A and G (1 and 7) showed cytotoxic activity against the HT-29 cancer cell line with IC50 values of 7.1 and 7.2 μM, respectively.
  13. Preparation and Preliminary Structure-Activity Relationship Studies of Schwarzinicine A Analogs as Vasorelaxant Agents
    Lee FK, Chan NJ, Krishnan P, Datu Abdul Salam DS, Chee XW, Muhamad A, et al.
    J Nat Prod, 2024 Apr 26;87(4):675-691.
    PMID: 38442031 DOI: 10.1021/acs.jnatprod.3c00707
    Schwarzinicines A-D, a series of alkaloids recently discovered from Ficus schwarzii, exhibit pronounced vasorelaxant activity in rat isolated aorta. Building on this finding, a concise synthesis of schwarzinicines A and B has been reported, allowing further investigations into their biological properties. Herein, a preliminary exploration of the chemical space surrounding the structure of schwarzinicine A (1) was carried out aiming to identify structural features that are essential for vasorelaxant activity. A total of 57 analogs were synthesized and tested for vasorelaxant activity in rat isolated aorta. Both efficacy (Emax) and potency (EC50) of these analogs were compared. In addition to identifying structural features that are required for activity or associated with potency enhancement effect, four analogs showed significant potency improvements of up to 40.2-fold when compared to 1. Molecular dynamics simulation of a tetrameric 44-bound transient receptor potential canonical-6 (TRPC6) protein indicated that 44 could potentially form important interactions with the residues Glu509, Asp530, Lys748, Arg758, and Tyr521. These results may serve as a foundation for guiding further structural optimization of the schwarzinicine A scaffold, aiming to discover even more potent analogs.
  14. Monomeric, Dimeric, and Trimeric Tropane Alkaloids from Pellacalyx saccardianus
    Chan ZY, Krishnan P, Modaresi SM, Hii LW, Mai CW, Lim WM, et al.
    J Nat Prod, 2021 08 27;84(8):2272-2281.
    PMID: 34342431 DOI: 10.1021/acs.jnatprod.1c00374
    Seven new tropane alkaloids, including five monomeric (1-5), one dimeric (6), and one trimeric (7) 3α-nortropane ester, along with two known monomeric nortropane alkaloids (8 and 9), were isolated from the leaves and bark of Pellacalyx saccardianus. Their structures, including the absolute configuration of the enantiomeric pair of (±)-6, were elucidated by comprehensive spectroscopic analyses. Alkaloids 6 and 7 showed cytotoxicity toward human pancreatic cancer cell lines (AsPC-1, BxPC3, PANC-1, and SW1990). Alkaloids 1, 4, and 9 induced a smooth muscle relaxation effect comparable to that of atropine (Emax 106.1 ± 7.5%, 97.0 ± 5.2%, 100.9 ± 1.4%, 111.7 ± 1.7%, respectively) on isolated rat tracheal rings.
  15. Fulltext Efficiency of newly formulated camptothecin with β-cyclodextrin-EDTA-Fe3O4 nanoparticle-conjugated nanocarriers as an anti-colon cancer (HT29) drug
    Krishnan P, Rajan M, Kumari S, Sakinah S, Priya SP, Amira F, et al.
    Sci Rep, 2017 09 08;7(1):10962.
    PMID: 28887536 DOI: 10.1038/s41598-017-09140-1
    Camptothecin (CPT) is an anti-cancer drug that effectively treats various cancers, including colon cancer. However, poor solubility and other drawbacks have restricted its chemotherapeutic potential. To overcome these restrictions, CPT was encapsulated in CEF (cyclodextrin-EDTA-FE3O4), a composite nanoparticle of magnetic iron oxide (Fe3O4), and β-cyclodextrin was cross-linked with ethylenediaminetetraacetic acid (EDTA). This formulation improved CPT's solubility and bioavailability for cancer cells. The use of magnetically responsive anti-cancer formulation is highly advantageous in cancer chemotherapy. The chemical characterisation of CPT-CEF was studied here. The ability of this nano-compound to induce apoptosis in HT29 colon cancer cells and A549 lung cancer cells was evaluated. The dose-dependent cytotoxicity of CPT-CEF was shown using MTT. Propidium iodide and Annexin V staining, mitochondrial membrane depolarisation (JC-1 dye), and caspase-3 activity were assayed to detect apoptosis in CPT-CEF-treated cancer cells. Cell cycle analysis also showed G1 phase arrest, which indicated possible synergistic effects of the nano-carrier. These study results show that CPT-CEF causes a dose-dependent cell viability reduction in HT29 and A549 cells and induces apoptosis in colon cancer cells via caspase-3 activation. These data strongly suggest that CPT could be used as a major nanocarrier for CPT to effectively treat colon cancer.
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