Displaying publications 1 - 20 of 88 in total

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  1. The protective effects of Zingiber zerumbet rhizome against fevers in rats
    Mohd Salleh H, Ablat A, Chong SL, Hazni H, Tohar N, Fauzi N, et al.
    Naturwissenschaften, 2024 Apr 01;111(2):20.
    PMID: 38558027 DOI: 10.1007/s00114-024-01907-7
    The Zingiber zerumbet rhizomes are traditionally used to treat fever, and the in vitro inhibitory effect of ethyl acetate extract from Zingiber zerumbet rhizomes (EAEZZR) against DENV2 NS2B/NS3 (two non-structural proteins, NS2 and NS3 of dengue virus type 2) has been reported earlier. This study was carried out to establish an acute toxicity profile and evaluate the anti-fever (anti-pyretic) activities of EAEZZR in yeast-induced fever in rats. The major compound of EAEZZR, zerumbone, was isolated using chromatographic methods including column chromatography (CC) and preparative thin-layer chromatography (PTLC). Additionally, the structure of zerumbone was elucidated using nuclear magnetic resonance (NMR), liquid chromatography mass spectrometer-ion trap-time of flight (LCMS-IT-TOF), infrared (IR), and ultraviolet (UV) spectroscopy. The toxicity of EAEZZR was evaluated using Organization for Economic Cooperation and Development Test Guideline 425 (OECD tg-425) with minor modifications at concentrations EAEZZR of 2000 mg/kg, 3000 mg/kg, and 5000 mg/kg. Anti-fever effect was determined by yeast-induced fever (pyrexia) in rats. The acute toxicity study showed that EAEZZR is safe at the highest 5000 mg/kg body weight dose in Sprague Dawley rats. Rats treated with EAEZZR at doses of 125, 250, and 500 mg/kg exhibited a significant reduction in rectal temperature (TR) in the first 1 h. EAEZZR at the lower dose of 125 mg/kg showed substantial potency against yeast-induced fever for up to 2 h compared to 0 h in controls. A significant reduction of TR was observed in rats treated with standard drug aspirin in the third through fourth hours. Based on the present findings, ethyl acetate extract of Zingiber zerumbet rhizomes could be considered safe up to the dose of 5000 mg/kg, and the identification of active ingredients of Zingiber zerumbet rhizomes may allow their use in the treatment of fever with dengue virus infection.
  2. Development, optimization and characterization of cisplatin loaded cubosomes for human lung carcinoma
    Umar H, Wahab HA, Ahmed N, Fujimura NA, Amjad MW, Bukhari SNA, et al.
    Drug Dev Ind Pharm, 2024 Mar 20.
    PMID: 38451066 DOI: 10.1080/03639045.2024.2326043
    OBJECTIVES: This study aimed to develop, optimize and evaluate glyceryl monooleate (GMO) based cubosomes as a drug delivery system containing cisplatin for treatment of human lung carcinoma.

    SIGNIFICANCE: The significance of this research was to successfully incorporate slightly water soluble and potent anticancer drug (cisplatin) into cubosomes, which provide slow and sustained release of drug for longer period of time.

    METHODS: The delivery system was developed through top-down approach by melting GMO and poloxamer 407 (P407) at 70 °C and then drop-wise addition of warm deionized water (70 °C) containing cisplatin. The formulation then exposed to probe sonicator for about 2 min. A randomized regular two level full factorial design with help of Design Expert was used for optimization of blank cubosomal formulations. Cisplatin loaded cubosomes were then subjected to physico-chemical characterization.

    RESULTS: The characterization of the formulation revealed that it had a sufficient surface charge of -9.56 ± 1.33 mV, 168.25 ± 5.73 nm particle size, and 60.64 ± 0.11% encapsulation efficiency. The in vitro release of cisplatin from the cubosomes at pH 7.4 was observed to be sustained, with 94.5% of the drug being released in 30 h. In contrast, 99% of cisplatin was released from the drug solution in just 1.5 h. In vitro cytotoxicity assay was conducted on the human lung carcinoma NCI-H226 cell line, the cytotoxicity of cisplatin-loaded cubosomes was relative to that of pure cisplatin solution, while blank (without cisplatin) cubosomes were nontoxic.

    CONCLUSIONS: The obtained results demonstrated the successful development of cubosomes for sustained delivery of cisplatin.

  3. Platinum-based targeted chemotherapies and reversal of cisplatin resistance in non-small cell lung cancer (NSCLC)
    Umar H, Wahab HA, Attiq A, Amjad MW, Bukhari SNA, Ahmad W
    Mutat Res, 2024 Mar 19;828:111856.
    PMID: 38520879 DOI: 10.1016/j.mrfmmm.2024.111856
    Lung cancer is the one of the most prevalent cancer in the world. It kills more people from cancer than any other cause and is especially common in underdeveloped nations. With 1.2 million instances, it is also the most prevalent cancer in men worldwide, making about 16.7% of the total cancer burden. Surgery is the main form of curative treatment for early-stage lung cancer. However, the majority of patients had incurable advanced non-small cell lung cancer (NSCLC) recurrence after curative purpose surgery, which is indicative of the aggressiveness of the illness and the dismal outlook. The gold standard of treatment for NSCLC patients includes drug targeting of specific mutated genes drive in development of lung cancer. Furthermore, patients with advanced NSCLC and those with early-stage illness needing adjuvant therapy should use cisplatin as it is the more active platinum drug. So, this review encompasses the non-small cell lung cancer microenvironment, treatment approaches, and use of cisplatin as a first-line regimen for NSCLC, its mechanism of action, cisplatin resistance in NSCLC and also the prevention strategies to revert the drug resistance.
  4. Fulltext Synthesis, biological activities, and evaluation molecular docking-dynamics studies of new phenylisoxazole quinoxalin-2-amine hybrids as potential α-amylase and α-glucosidase inhibitors
    Mohd Radzuan SN, Phongphane L, Abu Bakar MH, Che Omar MT, Nor Shahril NS, Supratman U, et al.
    RSC Adv, 2024 Feb 29;14(11):7684-7698.
    PMID: 38444963 DOI: 10.1039/d3ra08642a
    New phenylisoxazole quinoxalin-2-amine hybrids 5a-i were successfully synthesised with yields of 53-85% and characterised with various spectroscopy methods. The synthesised hybrids underwent in vitro α-amylase and α-glucosidase inhibitory assays, with acarbose as the positive control. Through the biological study, compound 5h exhibits the highest α-amylase inhibitory activity with IC50 = 16.4 ± 0.1 μM while compounds 5a-c, 5e and 5h exhibit great potential as α-glucosidase inhibitors, with 5c being the most potent (IC50 = 15.2 ± 0.3 μM). Among the compounds, 5h exhibits potential as a dual inhibitor for both α-amylase (IC50 = 16.4 ± 0.1 μM) and α-glucosidase (IC50 = 31.6 ± 0.4 μM) enzymes. Through the molecular docking studies, the inhibition potential of the selected compounds is supported. Compound 5h showed important interactions with α-amylase enzyme active sites and exhibited the highest binding energy of -8.9 ± 0.10 kcal mol-1, while compound 5c exhibited the highest binding energy of -9.0 ± 0.20 kcal mol-1 by forming important interactions with the α-glucosidase enzyme active sites. The molecular dynamics study showed that the selected compounds exhibited relative stability when binding with α-amylase and α-glucosidase enzymes. Additionally, compound 5h demonstrated a similar pattern of motion and mechanism of action as the commercially available miglitol.
  5. Breaking barriers: bilosomes gel potentials to pave the way for transdermal breast cancer treatment with Tamoxifen
    Abou Assi R, Abdulbaqi IM, Tan SM, Wahab HA, Darwis Y, Chan SY
    Drug Dev Ind Pharm, 2023 Sep 18.
    PMID: 37722711 DOI: 10.1080/03639045.2023.2256404
    OBJECTIVE: Breast cancer affects women globally, regardless of age or location. On the other hand, Tamoxifen (TXN), a class II biopharmaceutical drug is acting as a prophylactic/treating agent for women at risk of and/or with hormone receptor-positive breast cancer. However, its oral administration has life-threatening side effects, which have led researchers to investigate alternative delivery methods. One such method is transdermal drug delivery utilizing bile salts as penetration enhancers, aka Bilosomes.

    METHODS: Bilosomes formulations were optimized statistically for the outcome of vesicle shape, size, and entrapment efficiency using two types of bile, i.e. sodium taurocholate and sodium cholate. These bilosomes were then loaded into HPMC base gel and further characterized for their morphology, drug content, pH, viscosity, spreadability and eventually ex-vivo skin penetration and deposition studies.

    RESULTS: Findings showed that sodium cholate has superiority as a penetration enhancer over sodium taurocholate in terms of morphological characterizes, zeta potential, and cumulative amounts of tamoxifen permeated per unit area (15.13 ± 0.71 μg/cm2 and 6.51 ± 0.6 μg/cm2 respectively). In fact, bilosomes designed with sodium cholate provided around 9 folds of skin deposition compared to TXN non-bilosomal gel.

    CONCLUSION: Bilosomes gels could be a promising option for locally delivering tamoxifen to the breast through the skin, offering an encouraging transdermal solution.

  6. Fulltext Comparative Study of In Situ Gel Formulation Based on the Physico-Chemical Aspect: Systematic Review
    Kurniawansyah IS, Rusdiana T, Sopyan I, Desy Arya IF, Wahab HA, Nurzanah D
    Gels, 2023 Aug 10;9(8).
    PMID: 37623100 DOI: 10.3390/gels9080645
    In recent years, in situ gel delivery systems have received a great deal of attention among pharmacists. The in situ gelation mechanism has several advantages over ointments, the most notable being the ability to provide regular and continuous drug delivery with no impact on visual clarity. Bioavailability, penetration, duration, and maximum medication efficacy are all improved by this mechanism. Our review systematically synthesizes and discusses comparisons between three types of in situ gelling system according to their phase change performance based on the physicochemical aspect from publications indexed in the Pubmed, ResearchGate, Scopus, Elsevier, and Google Scholar databases. An optimal temperature-sensitive in situ gelling solution must have a phase change temperature greater than ambient temperature (25 °C) to be able to be readily delivered to the eye; hence, it was fabricated at 35 °C, which is the precorneal temperature. In a pH-sensitive gelling system, a gel develops immediately when the bio-stimuli come into contact with it. An in situ gelling system with ionic strength-triggered medication can also perhaps be used in optical drug-delivery mechanisms. In studies about the release behavior of drugs from in situ gels, different models have been used such as zero-order kinetics, first-order kinetics, the Higuchi model, and the Korsmeyer-Peppas, Peppas-Sahlin and Weibull models. In conclusion, the optimum triggering approach for forming gels in situ is determined by a certain therapeutic delivery application combined with the physico-chemical qualities sought.
  7. Fulltext In Vitro and In Silico Analysis of the Anticancer Effects of Eurycomanone and Eurycomalactone from Eurycoma longifolia
    Yunos NM, Wahab HA, Al-Thiabat MG, Sallehudin NJ, Jauri MH
    Plants (Basel), 2023 Jul 31;12(15).
    PMID: 37570981 DOI: 10.3390/plants12152827
    Eurycomanone and eurycomalactone are known quassinoids present in the roots and stems of Eurycoma longifolia. These compounds had been reported to have cytotoxic effects, however, their mechanism of action in a few cancer cell lines have yet to be elucidated. This study was aimed at investigating the anticancer effects and mechanisms of action of eurycomanone and eurycomalactone in cervical (HeLa), colorectal (HT29) and ovarian (A2780) cancer cell lines via Sulforhodamine B assay. Their mechanism of cell death was evaluated based on Hoechst 33342 assay and in silico molecular docking toward DHFR and TNF-α as putative protein targets. Eurycomanone and eurycomalactone exhibited in vitro anticancer effects manifesting IC50 values of 4.58 ± 0.090 µM and 1.60 ± 0.12 µM (HeLa), 1.22 ± 0.11 µM and 2.21 ± 0.049 µM (HT-29), and 1.37 ± 0.13 µM and 2.46 ± 0.081 µM (A2780), respectively. They induced apoptotic cancer cell death in dose- and time-dependent manners. Both eurycomanone and eurycomalactone were also predicted to have good inhibitory potential as demonstrated by the docking into TNF-α with binding affinity of -8.83 and -7.51 kcal/mol, respectively, as well as into DHFR with binding affinity results of -8.05 and -8.87 kcal/mol, respectively. These results support the evidence of eurycomanone and eurycomalactone as anticancer agents via apoptotic cell death mechanism that could be associated with TNF-α and DHFR inhibition as among possible protein targets.
  8. Fulltext Phaleria macrocarpa (Scheff.) Boerl.: An updated review of pharmacological effects, toxicity studies, and separation techniques
    Ahmad R, Khairul Nizam Mazlan M, Firdaus Abdul Aziz A, Mohd Gazzali A, Amir Rawa MS, Wahab HA
    Saudi Pharm J, 2023 Jun;31(6):874-888.
    PMID: 37234341 DOI: 10.1016/j.jsps.2023.04.006
    Phaleria macrocarpa (Scheff.) Boerl. is geographically distributed around Papua Island, Indonesia. Traditionally, P. macrocarpa is exercised to reduce pain, stomachache, diarrhea, tumor problems, blood glucose, cholesterol, and blood pressure. A growing interest in the medicinal values of P. macrocarpa especially in Asia reflects the usage of diverse extraction techniques, particularly modern approaches. In this review article, the extraction methods and solvents relevant to P. macrocarpa were discussed, with the extent of its pharmacological activities. Recent bibliographic databases such as Google Scholar, PubMed, and Elsevier between 2010 and 2022 were assessed. Based on the findings, the pharmacological studies of P. macrocarpa are still pertinent to its traditional uses but primarily emphasise anti-proliferative activity especially colon and breast cancer cells with low toxicity and fruit as the most studied plant part. The utilization of modern separation techniques has predominantly been aimed at extracting mangiferin and phenolic-rich compounds and evaluating their antioxidant capacity. However, the isolation of bioactive compounds remains a challenge, leading to the extensive utilization of the extracts in in vivo studies. This review endeavors to highlight modern extraction methods that could potentially be used as a point of reference in the future for exploring novel bioactive compounds and drug discovery on a multi-scale extraction level.
  9. tLyp-1: A peptide suitable to target NRP-1 receptor
    Larue L, Kenzhebayeva B, Al-Thiabat MG, Jouan-Hureaux V, Mohd-Gazzali A, Wahab HA, et al.
    Bioorg Chem, 2023 Jan;130:106200.
    PMID: 36332316 DOI: 10.1016/j.bioorg.2022.106200
    Targeting vascular endothelial growth factor receptor (VEFGR) and its co-receptor neuropilin-1 (NRP-1) is an interesting vascular strategy. tLyp-1 is a tumor-homing and penetrating peptide of 7 amino acids (CGNKRTR). It is a truncated form of Lyp-1 (CGNKRTRGC), which is known to target NRP-1 receptor, with high affinity and specificity. It is mediated by endocytosis via C-end rule (CendR) internalization pathway. The aim of this study is to evaluate the importance of each amino acid in the tLyp-1 sequence through alanine-scanning (Ala-scan) technique, during which each of the amino acid in the sequence was systematically replaced by alanine to produce 7 different analogues. In silico approach through molecular docking and molecular dynamics are employed to understand the interaction between the peptide and its analogues with the NRP-1 receptor, followed by in vitro ligand binding assay study. The C-terminal Arg is crucial in the interaction of tLyp-1 with NRP-1 receptor. Substituting this residue dramatically reduces the affinity of this peptide which is clearly seen in this study. Lys-4 is also important in the interaction, which is confirmed via the in vitro study and the MM-PBSA analysis. The finding in this study supports the CendR, in which the presence of R/K-XX-R/K motif is essential in the binding of a ligand with NRP-1 receptor. This presented work will serve as a guide in the future work pertaining the development of active targeting agent towards NRP-1 receptor.
  10. Fulltext Assessing the potential of NS2B/NS3 protease inhibitors biomarker in curbing dengue virus infections: In silico vs. In vitro approach
    Norshidah H, Leow CH, Ezleen KE, Wahab HA, Vignesh R, Rasul A, et al.
    Front Cell Infect Microbiol, 2023;13:1061937.
    PMID: 36864886 DOI: 10.3389/fcimb.2023.1061937
    An increase in the occurrence of viral infectious diseases is a global concern for human health. According to a WHO report, dengue virus (DENV) is one of the most common viral diseases affecting approximately 400 million people annually, with worsening symptoms in nearly 1% of cases. Both academic and industrial researchers have conducted numerous studies on viral epidemiology, virus structure and function, source and route of infection, treatment targets, vaccines, and drugs. The development of CYD-TDV or Dengvaxia® vaccine has been a major milestone in dengue treatment. However, evidence has shown that vaccines have some drawbacks and limitations. Therefore, researchers are developing dengue antivirals to curb infections. DENV NS2B/NS3 protease is a DENV enzyme essential for replication and virus assembly, making it an interesting antiviral target. For faster hit and lead recognition of DENV targets, methods to screen large number of molecules at lower costs are essential. Similarly, an integrated and multidisciplinary approach involving in silico screening and confirmation of biological activity is required. In this review, we discuss recent strategies for searching for novel DENV NS2B/NS3 protease inhibitors from the in silico and in vitro perspectives, either by applying one of the approaches or by integrating both. Therefore, we hope that our review will encourage researchers to integrate the best strategies and encourage further developments in this area.
  11. Fulltext Multi-population Black Hole Algorithm for the problem of data clustering
    Salih SQ, Alsewari AA, Wahab HA, Mohammed MKA, Rashid TA, Das D, et al.
    PLoS One, 2023;18(7):e0288044.
    PMID: 37406006 DOI: 10.1371/journal.pone.0288044
    The retrieval of important information from a dataset requires applying a special data mining technique known as data clustering (DC). DC classifies similar objects into a groups of similar characteristics. Clustering involves grouping the data around k-cluster centres that typically are selected randomly. Recently, the issues behind DC have called for a search for an alternative solution. Recently, a nature-based optimization algorithm named Black Hole Algorithm (BHA) was developed to address the several well-known optimization problems. The BHA is a metaheuristic (population-based) that mimics the event around the natural phenomena of black holes, whereby an individual star represents the potential solutions revolving around the solution space. The original BHA algorithm showed better performance compared to other algorithms when applied to a benchmark dataset, despite its poor exploration capability. Hence, this paper presents a multi-population version of BHA as a generalization of the BHA called MBHA wherein the performance of the algorithm is not dependent on the best-found solution but a set of generated best solutions. The method formulated was subjected to testing using a set of nine widespread and popular benchmark test functions. The ensuing experimental outcomes indicated the highly precise results generated by the method compared to BHA and comparable algorithms in the study, as well as excellent robustness. Furthermore, the proposed MBHA achieved a high rate of convergence on six real datasets (collected from the UCL machine learning lab), making it suitable for DC problems. Lastly, the evaluations conclusively indicated the appropriateness of the proposed algorithm to resolve DC issues.
  12. Celebrating Diversity, Equity, Inclusion, and Respect in Computational and Theoretical Chemistry
    Cournia Z, Soares TA, Wahab HA, Amaro RE
    J Chem Inf Model, 2022 Dec 26;62(24):6287-6291.
    PMID: 36567670 DOI: 10.1021/acs.jcim.2c01543
  13. Fulltext Fluorescent Multifunctional Organic Nanoparticles for Drug Delivery and Bioimaging: A Tutorial Review
    Vargas-Nadal G, Köber M, Nsamela A, Terenziani F, Sissa C, Pescina S, et al.
    Pharmaceutics, 2022 Nov 17;14(11).
    PMID: 36432688 DOI: 10.3390/pharmaceutics14112498
    Fluorescent organic nanoparticles (FONs) are a large family of nanostructures constituted by organic components that emit light in different spectral regions upon excitation, due to the presence of organic fluorophores. FONs are of great interest for numerous biological and medical applications, due to their high tunability in terms of composition, morphology, surface functionalization, and optical properties. Multifunctional FONs combine several functionalities in a single nanostructure (emission of light, carriers for drug-delivery, functionalization with targeting ligands, etc.), opening the possibility of using the same nanoparticle for diagnosis and therapy. The preparation, characterization, and application of these multifunctional FONs require a multidisciplinary approach. In this review, we present FONs following a tutorial approach, with the aim of providing a general overview of the different aspects of the design, preparation, and characterization of FONs. The review encompasses the most common FONs developed to date, the description of the most important features of fluorophores that determine the optical properties of FONs, an overview of the preparation methods and of the optical characterization techniques, and the description of the theoretical approaches that are currently adopted for modeling FONs. The last part of the review is devoted to a non-exhaustive selection of some recent biomedical applications of FONs.
  14. Fulltext Neuraminidase Inhibitor of Garcinia atroviridis L. Fruits and Leaves Using Partial Purification and Molecular Characterization
    Muchtaridi M, Nuwarda RF, Ikram EHK, Abdul Rahim AS, Gazzali AM, Wahab HA
    Molecules, 2022 Jan 30;27(3).
    PMID: 35164214 DOI: 10.3390/molecules27030949
    Neuraminidase (NA) is an enzyme that prevents virions from aggregating within the host cell and promotes cell-to-cell spread by cleaving glycosidic linkages to sialic acid. The best-known neuraminidase is the viral neuraminidase, which present in the influenza virus. Thus, the development of anti-influenza drugs that inhibit NA has emerged as an important and intriguing approach in the treatment of influenza. Garcinia atroviridis L. (GA) dried fruits (GAF) are used commercially as seasoning and in beverages. The main objective of this study was to identify a new potential neuraminidase inhibitor from GA. A bioassay-guided fractionation method was applied to obtain the bioactive compounds leading to the identification of garcinia acid and naringenin. In an enzyme inhibition study, garcinia acid demonstrated the highest activity when compared to naringenin. Garcinia acid had the highest activity, with an IC50 of 17.34-17.53 µg/mL or 91.22-92.21 µM against Clostridium perfringens-NA, and 56.71-57.85 µg/mL or 298.32-304.31 µM against H1N1-NA. Based on molecular docking results, garcinia acid interacted with the triad arginine residues (Arg118, Arg292, and Arg371) of the viral neuraminidase, implying that this compound has the potential to act as a NA enzyme inhibitor.
  15. Fulltext Computational study of nitro-benzylidene phenazine as dengue virus-2 NS2B-NS3 protease inhibitor
    Salin NH, Hariono M, Khalili NSD, Zakaria II, Saqallah FG, Mohamad Taib MNA, et al.
    Front Mol Biosci, 2022;9:875424.
    PMID: 36465554 DOI: 10.3389/fmolb.2022.875424
    According to the World Health Organisation (WHO), as of week 23 of 2022, there were more than 1,311 cases of dengue in Malaysia, with 13 deaths reported. Furthermore, there was an increase of 65.7% during the same period in 2021. Despite the increase in cumulative dengue incidence, there is no effective antiviral drug available for dengue treatment. This work aimed to evaluate several nitro-benzylidene phenazine compounds, especially those that contain 4-hydroxy-3,5-bis((2-(4-nitrophenyl)hydrazinylidene)-methyl)benzoate through pharmacophore queries selection method as potential dengue virus 2 (DENV2) NS2B-NS3 protease inhibitors. Herein, molecular docking was employed to correlate the energies of selected hits' free binding and their binding affinities. Pan assay interference compounds (PAINS) filter was also adopted to identify and assess the drug-likeness, toxicity, mutagenicity potentials, and pharmacokinetic profiles to select hit compounds that can be considered as lead DENV2 NS2B-NS3 protease inhibitors. Molecular dynamics assessment of two nitro-benzylidene phenazine derivatives bearing dinitro and hydroxy groups at the benzylidene ring showed their stability at the main binding pocket of DENV2 protease, where their MM-PBSA binding energies were between -22.53 and -17.01 kcal/mol. This work reports those two nitro-benzylidene phenazine derivatives as hits with 52-55% efficiency as antiviral candidates. Therefore, further optimisation is required to minimise the lead compounds' toxicity and mutagenicity.
  16. Advancing Women in Chemistry
    Cournia Z, Soares TA, Wahab HA, Amaro RE
    J Chem Inf Model, 2021 11 22;61(11):5305-5306.
    PMID: 34668709 DOI: 10.1021/acs.jcim.1c01185
  17. Fulltext Identification of Tropical Plant Extracts That Extend Yeast Chronological Life Span
    Kwong MMY, Lee JW, Samian MR, Wahab HA, Watanabe N, Ong EBB
    Cells, 2021 10 11;10(10).
    PMID: 34685698 DOI: 10.3390/cells10102718
    Certain plant extracts (PEs) contain bioactive compounds that have antioxidant and lifespan-extending activities on organisms. These PEs play different roles in cellular processes, such as enhancing stress resistance and modulating longevity-defined signaling pathways that contribute to longevity. Here, we report the discovery of PEs that extended chronological life span (CLS) in budding yeast from a screen of 222 PEs. We identified two PEs, the leaf extracts of Manihot esculenta and Wodyetia bifurcata that extended CLS in a dose-dependent manner. The CLS-extending PEs also conferred oxidative stress tolerance, suggesting that these PEs might extend yeast CLS through the upregulation of stress response pathways.
  18. Fulltext Conjugated β-Cyclodextrin Enhances the Affinity of Folic Acid towards FRα: Molecular Dynamics Study
    Al-Thiabat MG, Gazzali AM, Mohtar N, Murugaiyah V, Kamarulzaman EE, Yap BK, et al.
    Molecules, 2021 Aug 31;26(17).
    PMID: 34500740 DOI: 10.3390/molecules26175304
    Drug targeting is a progressive area of research with folate receptor alpha (FRα) receiving significant attention as a biological marker in cancer drug delivery. The binding affinity of folic acid (FA) to the FRα active site provides a basis for recognition of FRα. In this study, FA was conjugated to beta-cyclodextrin (βCD) and subjected to in silico analysis (molecular docking and molecular dynamics (MD) simulation (100 ns)) to investigate the affinity and stability for the conjugated system compared to unconjugated and apo systems (ligand free). Docking studies revealed that the conjugated FA bound into the active site of FRα with a docking score (free binding energy < -15 kcal/mol), with a similar binding pose to that of unconjugated FA. Subsequent analyses from molecular dynamics (MD) simulations, root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg) demonstrated that FA and FA-βCDs created more dynamically stable systems with FRα than the apo-FRα system. All systems reached equilibrium with stable RMSD values ranging from 1.9-2.4 Å and the average residual fluctuation values of the FRα backbone atoms for all residues (except for terminal residues ARG8, THR9, THR214, and LEU215) were less than 2.1 Å with a consistent Rg value of around 16.8 Å throughout the MD simulation time (0-100 ns). The conjugation with βCD improved the stability and decreased the mobility of all the residues (except residues 149-151) compared to FA-FRα and apo-FRα systems. Further analysis of H-bonds, binding free energy (MM-PBSA), and per residue decomposition energy revealed that besides APS81, residues HIS20, TRP102, HIS135, TRP138, TRP140, and TRP171 were shown to have more favourable energy contributions in the holo systems than in the apo-FRα system, and these residues might have a direct role in increasing the stability of holo systems.
  19. Identification of 1,2,4-Triazolylthioethanone Scaffold for the Design of New Acetylcholinesterase Inhibitors
    Fatiha Muhammad E, Kumar A, Wahab HA, Zhang KYJ
    Mol Inform, 2021 08;40(8):e2100020.
    PMID: 34060234 DOI: 10.1002/minf.202100020
    Acetylcholinesterase (AChE) inhibitors are the most effective drugs for Alzheimer's disease treatment. However, considering the potential and failure rates of AChE inhibitors, chemical scaffolds targeting cholinesterase specifically are still very limited. Herein, we report a new class of AChE inhibitors identified by employing a virtual screening approach that combines shape similarity with molecular docking calculations. Virtual screening followed by the evaluation of AChE inhibitory activity allowed us to identify 1,2,4-triazolylthioethanones as a novel class of AChE inhibitors. Thirteen compounds with 1,2,4-triazolylthiothanone core and IC50 values in the range of 0.15±0.07 to 3.32±0.92 μM have been reported here. Our findings shed light into a class of AChE inhibitors that could be useful starting point for the development of novel therapeutics to tackle Alzheimer's disease.
  20. Zealpeptaibolin, an 11-mer cytotoxic peptaibol group with 3 Aib-Pro motifs isolated from Trichoderma sp. RK10-F026
    Rawa MSA, Nogawa T, Okano A, Futamura Y, Wahab HA, Osada H
    J Antibiot (Tokyo), 2021 08;74(8):485-495.
    PMID: 34163024 DOI: 10.1038/s41429-021-00429-y
    Six new 11-mer peptaibols designed as zealpeptaibolins, A - F were isolated from the soil fungus, Trichoderma sp. RK10-F026, based on the principal component analysis of the MS data from five different culture compositions. Previously, 20-mer peptaibols from the same fungal strain were identified; 11-mer peptaibols in contrast were discovered from a different culture condition, signifying peptaibol production was culture condition-dependent. These peptaibols contained three Aib-Pro motifs in the sequence. The structures were established by NMR and HR-MS experiments including detailed MS/MS fragmentations. The absolute configurations were determined by Marfey's analysis. Zealpeptaibolin F exhibited the strongest cytotoxicity toward K562 leukemia cells with an IC50 value of 0.91 µM.
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