Displaying publications 61 - 80 of 177 in total

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  1. Quantum probability ranking principle for ligand-based virtual screening
    Al-Dabbagh MM, Salim N, Himmat M, Ahmed A, Saeed F
    J Comput Aided Mol Des, 2017 Apr;31(4):365-378.
    PMID: 28220440 DOI: 10.1007/s10822-016-0003-4
    Chemical libraries contain thousands of compounds that need screening, which increases the need for computational methods that can rank or prioritize compounds. The tools of virtual screening are widely exploited to enhance the cost effectiveness of lead drug discovery programs by ranking chemical compounds databases in decreasing probability of biological activity based upon probability ranking principle (PRP). In this paper, we developed a novel ranking approach for molecular compounds inspired by quantum mechanics, called quantum probability ranking principle (QPRP). The QPRP ranking criteria would make an attempt to draw an analogy between the physical experiment and molecular structure ranking process for 2D fingerprints in ligand based virtual screening (LBVS). The development of QPRP criteria in LBVS has employed the concepts of quantum at three different levels, firstly at representation level, this model makes an effort to develop a new framework of molecular representation by connecting the molecular compounds with mathematical quantum space. Secondly, estimate the similarity between chemical libraries and references based on quantum-based similarity searching method. Finally, rank the molecules using QPRP approach. Simulated virtual screening experiments with MDL drug data report (MDDR) data sets showed that QPRP outperformed the classical ranking principle (PRP) for molecular chemical compounds.
    Matched MeSH terms: Drug Discovery/methods*
  2. Emerging frontiers of deep eutectic solvents in drug discovery and drug delivery systems
    Zainal-Abidin MH, Hayyan M, Ngoh GC, Wong WF, Looi CY
    J Control Release, 2019 12 28;316:168-195.
    PMID: 31669211 DOI: 10.1016/j.jconrel.2019.09.019
    The applications of eutectic systems, including deep eutectic solvents (DESs), in diverse sectors have drawn significant interest from researchers, academicians, engineers, medical scientists, and pharmacists. Eutecticity increases drug dissolution, improves drug penetration, and acts as a synthesis route for drug carriers. To date, DESs have been extensively explored as potential drug delivery systems on account of their unique properties such as tunability and chemical and thermal stability. This review discusses two major topics: first, the application of eutectic mixtures (before and after the introduction of DES) in the field of drug delivery systems, and second, the most promising examples of DES pharmaceutical activity. It also considers future prospects in the medical and biotechnological fields. In addition to the application of DESs in drug delivery systems, they show greatly promising pharmaceutical activities, including anti-fungal, anti-bacterial, anti-viral, and anti-cancer activities. Eutecticity is a valid strategy for overcoming many obstacles inherently associated with either introducing new drugs or enhancing drug delivery systems.
    Matched MeSH terms: Drug Discovery/methods
  3. Current Technology in the Discovery and Development of Novel Antibacterials
    Chung PY
    Curr Drug Targets, 2018;19(7):832-840.
    PMID: 28891454 DOI: 10.2174/1389450118666170911114604
    BACKGROUND: Bacterial resistance to antibiotics is one of the most serious challenge to global public health. The introduction of new antibiotics in clinical settings, i.e. agents that belong to a new class of antibacterials, act on new targets or has a novel mechanisms of action, may not be sufficient to cope with the emergence of multidrug-resistant pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and Escherichia coli, which are increasingly prevalent in healthcare settings in Europe, the USA and Asia. Hence, coordinated efforts in minimizing the risk of spread of resistant bacteria and renewing research efforts in the search for novel antibacterial agents are urgently needed to manage this global crisis.

    OBJECTIVE: This review highlights the challenges and potential in using current technologies in the discovery and development of novel antibacterial agents to keep up with the constantly evolving resistance in bacteria.

    CONCLUSION: With the explosion of bacterial genomic data and rapid development of new sequencing technologies, the understanding of bacterial pathogenesis and identification of novel antibiotic targets have significantly improved.

    Matched MeSH terms: Drug Discovery/methods
  4. Fulltext Current progress of immunoinformatics approach harnessed for cellular- and antibody-dependent vaccine design
    Kazi A, Chuah C, Majeed ABA, Leow CH, Lim BH, Leow CY
    Pathog Glob Health, 2018 05;112(3):123-131.
    PMID: 29528265 DOI: 10.1080/20477724.2018.1446773
    Immunoinformatics plays a pivotal role in vaccine design, immunodiagnostic development, and antibody production. In the past, antibody design and vaccine development depended exclusively on immunological experiments which are relatively expensive and time-consuming. However, recent advances in the field of immunological bioinformatics have provided feasible tools which can be used to lessen the time and cost required for vaccine and antibody development. This approach allows the selection of immunogenic regions from the pathogen genomes. The ideal regions could be developed as potential vaccine candidates to trigger protective immune responses in the hosts. At present, epitope-based vaccines are attractive concepts which have been successfully trailed to develop vaccines which target rapidly mutating pathogens. In this article, we provide an overview of the current progress of immunoinformatics and their applications in the vaccine design, immune system modeling and therapeutics.
    Matched MeSH terms: Drug Discovery/methods*
  5. Fulltext Phytochemical Constituents and Biological Activities of Melicope lunu-ankenda
    Eliaser EM, Ho JH, Hashim NM, Rukayadi Y, Ee GCL, Razis AFA
    Molecules, 2018 Oct 20;23(10).
    PMID: 30347850 DOI: 10.3390/molecules23102708
    Natural products, either pure compounds or standardized plant extracts, have provided opportunities for the discovery of new drugs. Nowadays, most of the world's population still relies on traditional medicines for healthcare purposes. Plants, in particular, are always used as traditional medicine, as they contain a diverse number of phytochemicals that can be used for the treatment of diseases. The multicomponent feature in the plants is considered a positive phytotherapeutic hallmark. Hence, ethnopharmacognosy has been the focus for finding alternative treatments for diseases. Melicope lunu-ankenda, also known as Euodia lunu-ankenda, is widely distributed in tropical regions of Asia. Different parts of M. lunu-ankenda have been used for treatment of hypertension, menstrual disorder, diabetes, and fever, and as an emmenagogue and tonic. It has also been consumed as salad and as a condiment for food flavorings. The justification of use of M. lunu-ankenda in folk medicines is supported by its reported biological activities, including its cytotoxic, antibacterial, antioxidant, analgesic, antidiabetic, and anti-inflammatory activities. This review summarizes the phytochemical compounds isolated from various parts of M. lunu-ankenda, such as root and leaves, and also its biological activities, which could make the species a new therapeutic agent for some diseases, including diabetes, in the future.
    Matched MeSH terms: Drug Discovery*
  6. Fulltext Anticancer Drug Discovery from Microbial Sources: The Unique Mangrove Streptomycetes
    Law JW, Law LN, Letchumanan V, Tan LT, Wong SH, Chan KG, et al.
    Molecules, 2020 Nov 17;25(22).
    PMID: 33212836 DOI: 10.3390/molecules25225365
    Worldwide cancer incidence and mortality have always been a concern to the community. The cancer mortality rate has generally declined over the years; however, there is still an increased mortality rate in poorer countries that receives considerable attention from healthcare professionals. This suggested the importance of the prompt detection, effective treatment, and prevention strategies. The genus Streptomyces has been documented as a prolific producer of biologically active secondary metabolites. Streptomycetes from mangrove environments attract researchers' attention due to their ability to synthesize diverse, interesting bioactive metabolites. The present review highlights research on mangrove-derived streptomycetes and the production of anticancer-related compounds from these microorganisms. Research studies conducted between 2008 and 2019, specifically mentioning the isolation of streptomycetes from mangrove areas and described the successful purification of compound(s) or generation of crude extracts with cytotoxic activity against human cancer cell lines, were compiled in this review. It is anticipated that there will be an increase in prospects for mangrove-derived streptomycetes as one of the natural resources for the isolation of chemotherapeutic agents.
    Matched MeSH terms: Drug Discovery*
  7. Fulltext Nano based drug delivery systems: recent developments and future prospects
    Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al.
    J Nanobiotechnology, 2018 Sep 19;16(1):71.
    PMID: 30231877 DOI: 10.1186/s12951-018-0392-8
    Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner. Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc.) in the treatment of various diseases. The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker molecules. The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed. In addition, we have included information regarding the trends and perspectives in nanomedicine area.
    Matched MeSH terms: Drug Discovery/methods
  8. Anti- COVID-19 drug discovery by flavonoid derivatives: an extensive computational drug design approach
    Banerjee S, Mukherjee S, Mohsin Kazi, Sen KK, Das A, Hasan R, et al.
    Cell Mol Biol (Noisy-le-grand), 2024 Sep 08;70(8):39-49.
    PMID: 39262264 DOI: 10.14715/cmb/2024.70.8.5
    The present study deals with the in-silico analyses of several flavonoid derivatives to explore COVID-19 through pharmacophore modelling, molecular docking, molecular dynamics, drug-likeness, and ADME properties. The initial literature study revealed that many flavonoids, including luteolin, quercetin, kaempferol, and baicalin may be useful against SARS β-coronaviruses, prompting the selection of their potential derivatives to investigate their abilities as inhibitors of COVID-19. The findings were streamlined using in silico molecular docking, which revealed promising energy-binding interactions between all flavonoid derivatives and the targeted protein. Notably, compounds 8, 9, 13, and 15 demonstrated higher potency against the coronavirus Mpro protein (PDB ID 6M2N). Compound 8 has a -7.2 Kcal/mol affinity for the protein and binds to it by hydrogen bonding with Gln192 and π-sulfur bonding with Met-165. Compound 9 exhibited a significant interaction with the main protease, demonstrating an affinity of -7.9 kcal/mol. Gln-192, Glu-189, Pro-168, and His-41 were the principle amino acid residues involved in this interaction. The docking score for compound 13 is -7.5 Kcal/mol, and it binds to the protease enzyme by making interactions with Leu-41, π-sigma, and Gln-189. These interactions include hydrogen bonding and π-sulfur. The major protease and compound 15 were found to bind with a favourable affinity of -6.8 Kcal/mol. This finding was further validated through molecular dynamic simulation for 1ns, analysing parameters such as RMSD, RMSF, and RoG profiles. The RoG values for all four of the compounds varied significantly (35.2-36.4). The results demonstrated the stability of the selected compounds during the simulation. After passing the stability testing, the compounds underwent screening for ADME and drug-likeness properties, fulfilling all the necessary criteria. The findings of the study may support further efforts for the discovery and development of safe drugs to treat COVID-19.
    Matched MeSH terms: Drug Discovery/methods
  9. Fulltext Discovery of anti-Ebola virus multi-target inhibitors from traditional Chinese medicine database using molecular screening, biophysical investigation, and binding free energy calculations
    Khan A, Sayaf AM, Mohammad A, Alshabrmi FM, Benameur T, Wei DQ, et al.
    J Infect Public Health, 2025 Feb;18(2):102636.
    PMID: 39798213 DOI: 10.1016/j.jiph.2024.102636
    INTRODUCTION: Ebola virus (EBOV) is a highly lethal RNA virus that causes severe hemorrhagic fever in humans and non-human primates. The lack of effective treatment or vaccine for this pathogen poses a serious threat to a global pandemic. Therefore, it is imperative to explore new drugs and therapies to combat this life-threatening infection.

    MATERIALS AND METHODS: In this study, we employed in silico methods to assess the inhibitory activity of natural products from traditional Chinese medicine (TCM) against four EBOV proteins that are crucial for viral replication and assembly: VP40, VP35, VP30, and VP24. We performed molecular docking of TCM compounds with the EBOV proteins and screened them based on their docking scores, binding free energies, and pharmacokinetic properties.

    RESULTS: Our results pinpointed eight TCM compounds (TCM1797, TCM2872, TCM250, TCM2837, TCM2644, TCM4697, TCM2322, and TCM277) that exhibited superior efficacy in inhibiting all the EBOV proteins compared to the controls. These compounds interacted with key residues of the EBOV proteins through various types of bonds, such as hydrogen bonds, salt bridges, and π-π interactions, forming stable complexes that could disrupt the function of the EBOV proteins. These compounds were found to possess known antiviral activity, acceptable pharmacokinetic properties, and human usage history, which make them promising candidates for anti-EBOV drug development. Moreover, the molecular simulation analysis confirmed the binding stability, structural compactness, and residue flexibility properties of these compounds. Furthermore, the binding free energy results revealed that VP30-TCM2644, VP30-TCM4697, VP35-TCM2837, VP24-TCM250, and VP24-TCM277 complexes exhibit significant binding free energy values compared to the control ligands. Principal Component Analysis (PCA) and Free Energy Landscape (FEL) results revealed the trajectories' motion and conformational energy states.

    CONCLUSIONS: Our findings provide valuable insights into the molecular mechanisms driving the efficacy of TCM drugs against EBOV and suggest novel approaches for the development of anti-EBOV therapies.

    Matched MeSH terms: Drug Discovery/methods
  10. Fulltext Ringing medicinal chemistry: The importance of 3-membered rings in drug discovery
    Uthumange SS, Liew AJH, Chee XW, Yeong KY
    Bioorg Med Chem, 2024 Dec 15;116:117980.
    PMID: 39536361 DOI: 10.1016/j.bmc.2024.117980
    Scaffold-based drug design has become increasingly prominent in the pharmaceutical field due to the systematic and effective approach through which it facilitates the development of novel drugs. The identification of key scaffolds provides medicinal chemists with a fundamental framework for subsequent research. With mounting evidence suggesting that increased aromaticity could impede the chances of developmental success for oral drug candidates, there is an imperative need for a more thorough exploration of alternative ring systems to mitigate attrition risks. The unique characteristics exhibited by three-membered rings have led to their application in medicinal chemistry. This review explores the use of cyclopropane-, aziridine-, thiirane-, and epoxide-containing compounds in drug discovery, focusing on their roles in approved medicines and drug candidates. Specifically, the importance of the three-membered ring systems in rending biological activity for each drug molecule was highlighted. The undeniable therapeutic value and intriguing features presented by these compounds suggest significant pharmacological potential, providing justification for their incorporation into the design of novel drug candidates.
    Matched MeSH terms: Drug Discovery*
  11. Fulltext Molecular modulators of celastrol as the keystones for its diverse pharmacological activities
    Ng SW, Chan Y, Chellappan DK, Madheswaran T, Zeeshan F, Chan YL, et al.
    Biomed Pharmacother, 2019 Jan;109:1785-1792.
    PMID: 30551432 DOI: 10.1016/j.biopha.2018.11.051
    In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.
    Matched MeSH terms: Drug Discovery/methods*; Drug Discovery/trends
  12. Fulltext The E-Cadherin and N-Cadherin Switch in Epithelial-to-Mesenchymal Transition: Signaling, Therapeutic Implications, and Challenges
    Loh CY, Chai JY, Tang TF, Wong WF, Sethi G, Shanmugam MK, et al.
    Cells, 2019 Sep 20;8(10).
    PMID: 31547193 DOI: 10.3390/cells8101118
    Epithelial-to-Mesenchymal Transition (EMT) has been shown to be crucial in tumorigenesis where the EMT program enhances metastasis, chemoresistance and tumor stemness. Due to its emerging role as a pivotal driver of tumorigenesis, targeting EMT is of great therapeutic interest in counteracting metastasis and chemoresistance in cancer patients. The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin, and this process is regulated by a complex network of signaling pathways and transcription factors. In this review, we summarized the recent understanding of the roles of E- and N-cadherins in cancer invasion and metastasis as well as the crosstalk with other signaling pathways involved in EMT. We also highlighted a few natural compounds with potential anti-EMT property and outlined the future directions in the development of novel intervention in human cancer treatments. We have reviewed 287 published papers related to this topic and identified some of the challenges faced in translating the discovery work from bench to bedside.
    Matched MeSH terms: Drug Discovery/methods; Drug Discovery/trends
  13. Fulltext Tinospora crispa (L.) Hook. f. & Thomson: A Review of Its Ethnobotanical, Phytochemical, and Pharmacological Aspects
    Ahmad W, Jantan I, Bukhari SN
    Front Pharmacol, 2016;7:59.
    PMID: 27047378 DOI: 10.3389/fphar.2016.00059
    Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae), found in the rainforests or mixed deciduous forests in Asia and Africa, is used in traditional medicines to treat numerous health conditions. This review summarizes the up-to-date reports about the ethnobotany, phytochemistry, pharmacological activities, toxicology, and clinical trials of the plant. It also provides critical assessment about the present knowledge of the plant which could contribute toward improving its prospect as a source of lead molecules for drug discovery. The plant has been used traditionally in the treatment of jaundice, rheumatism, urinary disorders, fever, malaria, diabetes, internal inflammation, fracture, scabies, hypertension, reducing thirst, increasing appetite, cooling down the body temperature, and maintaining good health. Phytochemical analyses of T. crispa revealed the presence of alkaloids, flavonoids, and flavone glycosides, triterpenes, diterpenes and diterpene glycosides, cis clerodane-type furanoditerpenoids, lactones, sterols, lignans, and nucleosides. Studies showed that the crude extracts and isolated compounds of T. crispa possessed a broad range of pharmacological activities such as anti-inflammatory, antioxidant, immunomodulatory, cytotoxic, antimalarial, cardioprotective, and anti-diabetic activities. Most pharmacological studies were based on crude extracts of the plant and the bioactive compounds responsible for the bioactivities have not been well identified. Further investigations are required to transform the experience-based claims on the use of T. crispa in traditional medicine practices into evidence-based information. The plant extract used in pharmacological and biological studies should be qualitatively and quantitatively analyzed based on its biomarkers. There should be detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more elaborate toxicity study to ensure safety of the plant for human use. More clinical trials are encouraged to be carried out if there are sufficient preclinical and safety data.
    Matched MeSH terms: Drug Discovery
  14. Fulltext In Vivo Anti-Tumor Effects of Citral on 4T1 Breast Cancer Cells via Induction of Apoptosis and Downregulation of Aldehyde Dehydrogenase Activity
    Nigjeh SE, Yeap SK, Nordin N, Rahman H, Rosli R
    Molecules, 2019 Sep 05;24(18).
    PMID: 31492037 DOI: 10.3390/molecules24183241
    Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females globally. The tumorigenic activities of cancer cells such as aldehyde dehydrogenase (ALDH) activity and differentiation have contributed to relapse and eventual mortality in breast cancer. Thus, current drug discovery research is focused on targeting breast cancer cells with ALDH activity and their capacity to form secondary tumors. Citral (3,7-dimethyl-2,6-octadienal), from lemon grass (Cymbopogoncitrates), has been previously reported to have a cytotoxic effect on breast cancer cells. Hence, this study was conducted to evaluate the in vivo effect of citral in targeting ALDH activity of breast cancer cells. BALB/c mice were challenged with 4T1 breast cancer cells followed by daily oral feeding of 50 mg/kg citral or distilled water for two weeks. The population of ALDH+ tumor cells and their capacity to form secondary tumors in both untreated and citral treated 4T1 challenged mice were assessed by Aldefluor assay and tumor growth upon cell reimplantation in normal mice, respectively. Citral treatment reduced the size and number of cells with ALDH+ activity of the tumors in 4T1-challenged BALB/c mice. Moreover, citral-treated mice were also observed with smaller tumor size and delayed tumorigenicity after reimplantation of the primary tumor cells into normal mice. These findings support the antitumor effect of citral in targeting ALDH+ cells and tumor recurrence in breast cancer cells.
    Matched MeSH terms: Drug Discovery
  15. Fulltext Biological Activities of Snowdrop (Galanthus spp., Family Amaryllidaceae)
    Kong CK, Low LE, Siew WS, Yap WH, Khaw KY, Ming LC, et al.
    Front Pharmacol, 2020;11:552453.
    PMID: 33679383 DOI: 10.3389/fphar.2020.552453
    Snowdrop is an iconic early spring flowering plant of the genus Galanthus (Amaryllidaceae). Galanthus species (Galanthus spp.) are economically important plants as ornaments. Galanthus spp has gained significance scientific and commercial interest due to the discovery of Galanthamine as symptomatic treatment drug for Alzhiermer disease. This review aims to discuss the bioactivities of Galanthus spp including anticholinesterase, antimicrobial, antioxidant and anticancer potential of the extracts and chemical constituents of Galanthus spp. This review highlights that Galanthus spp. as the exciting sources for drug discovery and nutraceutical development.
    Matched MeSH terms: Drug Discovery
  16. Fulltext Sinensetin: An Insight on Its Pharmacological Activities, Mechanisms of Action and Toxicity
    Han Jie L, Jantan I, Yusoff SD, Jalil J, Husain K
    Front Pharmacol, 2020;11:553404.
    PMID: 33628166 DOI: 10.3389/fphar.2020.553404
    Sinensetin, a plant-derived polymethoxylated flavonoid found in Orthosiphon aristatus var. aristatus and several citrus fruits, has been found to possess strong anticancer activities and a variety of other pharmacological benefits and promising potency in intended activities with minimal toxicity. This review aims to compile an up-to-date reports of published scientific information on sinensetin pharmacological activities, mechanisms of action and toxicity. The present findings about the compound are critically analyzed and its prospect as a lead molecule for drug discovery is highlighted. The databases employed for data collection are mainly through Google Scholar, PubMed, Scopus and Science Direct. In-vitro and in-vivo studies showed that sinensetin possessed strong anticancer activities and a wide range of pharmacological activities such as anti-inflammatory, antioxidant, antimicrobial, anti-obesity, anti-dementia and vasorelaxant activities. The studies provided some insights on its several mechanisms of action in cancer and other disease states. However, more detail mechanistic studies are needed to understand its pharmacological effects. More in vivo studies in various animal models including toxicity, pharmacokinetic, pharmacodynamic and bioavailability studies are required to assess its efficacy and safety before submission to clinical studies. In this review, an insight on sinensetin pharmacological activities and mechanisms of action serves as a useful resource for a more thorough and comprehensive understanding of sinensetin as a potential lead candidate for drug discovery.
    Matched MeSH terms: Drug Discovery
  17. Fulltext Metabolite profiling of endophytic Streptomyces spp. and its antiplasmodial potential
    Ahmad SJ, Mohamad Zin N, Mazlan NW, Baharum SN, Baba MS, Lau YL
    PeerJ, 2021;9:e10816.
    PMID: 33777509 DOI: 10.7717/peerj.10816
    Background: Antiplasmodial drug discovery is significant especially from natural sources such as plant bacteria. This research aimed to determine antiplasmodial metabolites of Streptomyces spp. against Plasmodium falciparum 3D7 by using a metabolomics approach.

    Methods: Streptomyces strains' growth curves, namely SUK 12 and SUK 48, were measured and P. falciparum 3D7 IC50 values were calculated. Metabolomics analysis was conducted on both strains' mid-exponential and stationary phase extracts.

    Results: The most successful antiplasmodial activity of SUK 12 and SUK 48 extracts shown to be at the stationary phase with IC50 values of 0.8168 ng/mL and 0.1963 ng/mL, respectively. In contrast, the IC50 value of chloroquine diphosphate (CQ) for antiplasmodial activity was 0.2812 ng/mL. The univariate analysis revealed that 854 metabolites and 14, 44 and three metabolites showed significant differences in terms of strain, fermentation phase, and their interactions. Orthogonal partial least square-discriminant analysis and S-loading plot putatively identified pavettine, aurantioclavine, and 4-butyldiphenylmethane as significant outliers from the stationary phase of SUK 48. For potential isolation, metabolomics approach may be used as a preliminary approach to rapidly track and identify the presence of antimalarial metabolites before any isolation and purification can be done.

    Matched MeSH terms: Drug Discovery
  18. Fulltext Plasmodium knowlesi exhibits distinct in vitro drug susceptibility profiles from those of Plasmodium falciparum
    van Schalkwyk DA, Blasco B, Davina Nuñez R, Liew JWK, Amir A, Lau YL, et al.
    Int J Parasitol Drugs Drug Resist, 2019 04;9:93-99.
    PMID: 30831468 DOI: 10.1016/j.ijpddr.2019.02.004
    New antimalarial agents are identified and developed after extensive testing on Plasmodium falciparum parasites that can be grown in vitro. These susceptibility studies are important to inform lead optimisation and support further drug development. Until recently, little was known about the susceptibility of non-falciparum species as these had not been adapted to in vitro culture. The recent culture adaptation of P. knowlesi has therefore offered an opportunity to routinely define the drug susceptibility of this species, which is phylogenetically closer to all other human malarias than is P. falciparum. We compared the in vitro susceptibility of P. knowlesi and P. falciparum to a range of established and novel antimalarial agents under identical assay conditions. We demonstrated that P. knowlesi is significantly less susceptible than P. falciparum to six of the compounds tested; and notably these include three ATP4 inhibitors currently under development as novel antimalarial agents, and one investigational antimalarial, AN13762, which is 67 fold less effective against P. knowlesi. For the other compounds there was a less than two-fold difference in susceptibility between species. We then compared the susceptibility of a recent P. knowlesi isolate, UM01, to that of the well-established, older A1-H.1 clone. This recent isolate showed similar in vitro drug susceptibility to the A1-H.1 clone, supporting the ongoing use of the better characterised clone to further study drug susceptibility. Lastly, we used isobologram analysis to explore the interaction of a selection of drug combinations and showed similar drug interactions across species. The species differences in drug susceptibility reported by us here and previously, support adding in vitro drug screens against P. knowlesi to those using P. falciparum strains to inform new drug discovery and lead optimisation.
    Matched MeSH terms: Drug Discovery
  19. Fulltext Natural Bioactive Thiazole-Based Peptides from Marine Resources: Structural and Pharmacological Aspects
    Dahiya R, Dahiya S, Fuloria NK, Kumar S, Mourya R, Chennupati SV, et al.
    Mar Drugs, 2020 Jun 24;18(6).
    PMID: 32599909 DOI: 10.3390/md18060329
    Peptides are distinctive biomacromolecules that demonstrate potential cytotoxicity and diversified bioactivities against a variety of microorganisms including bacteria, mycobacteria, and fungi via their unique mechanisms of action. Among broad-ranging pharmacologically active peptides, natural marine-originated thiazole-based oligopeptides possess peculiar structural features along with a wide spectrum of exceptional and potent bioproperties. Because of their complex nature and size divergence, thiazole-based peptides (TBPs) bestow a pivotal chemical platform in drug discovery processes to generate competent scaffolds for regulating allosteric binding sites and peptide-peptide interactions. The present study dissertates on the natural reservoirs and exclusive structural components of marine-originated TBPs, with a special focus on their most pertinent pharmacological profiles, which may impart vital resources for the development of novel peptide-based therapeutic agents.
    Matched MeSH terms: Drug Discovery
  20. Natural cyclic polypeptides as vital phytochemical constituents from seeds of selected medicinal plants
    Dahiya R, Dahiya S, Shrivastava J, Fuloria NK, Gautam H, Mourya R, et al.
    Arch Pharm (Weinheim), 2021 Feb 01.
    PMID: 33522644 DOI: 10.1002/ardp.202000446
    Cyclopolypeptides are among the most predominant biomolecules in nature, especially those derived from plant seeds. This category of compounds has gained extraordinary attention due to remarkable variety of structures and valuable biofunctions. These congeners display enormous variation in terms of both structure and function and are the most significant biomolecules due to their widespread bioproperties. The estrogenic activity, immunosuppressive activity, cytotoxicity, vasorelaxant activity, and other properties possessed by cyclic peptides from seeds of plants make these congeners attractive leads for the drug discovery process. The current study covers the important structural features, structure-activity relationship, synthesis methods, and bioproperties of plant seeds-originated bioactive peptides from Vaccaria segetalis, Linum usitatissimum, and Goniothalamus leiocarpus, which may prove vital for the development of novel therapeutics based on a peptide skeleton.
    Matched MeSH terms: Drug Discovery
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