Review
Pharmacology & Pharmacy
Khalil Saadeh, Nakulan Nantha Kumar, Ibrahim Talal Fazmin, Charlotte E. Edling, Kamalan Jeevaratnam
Summary: Malaria remains the leading cause of parasitic death worldwide, and artemisinin resistance poses a significant threat, necessitating the development of new combination therapies. Prior to widespread use, it is crucial to thoroughly investigate the safety of anti-malarial drugs, with a focus on cardiotoxicity. This research aims to clarify the potential mechanisms by which these drugs contribute to arrhythmias, providing important insights for assessing drug safety, stratifying patients based on arrhythmic risk, and guiding future anti-malarial drug development.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Juhi Khurana, Ashish Shrivastava, Ashutosh Singh, Ashish Gupta
Summary: This study evaluated the potential of PfRUVBLs (AAA family member proteins) as novel anti-malarial drug targets using computational approaches. Virtual screening and docking led to the identification of compounds that showed affinity for the active region of PfRUVBL1 protein. These compounds have the potential to be potent inhibitors of PfRUVBL1 protein and can be further tested for anti-malarial activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Viharika Bobba, Yaxin Li, Marjia Afrin, Raina Dano, Wenjing Zhang, Bibo Li, Bin Su
Summary: Researchers have developed a selective drug candidate library for the treatment of Human African trypanosomiasis. One compound in particular has shown high potency and selectively inhibits the growth of trypanosome cells. Further studies will guide future optimization efforts.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Shikha Sharma, Md Ehesan Ali
Summary: Plasmodium falciparum develops resistance to artemisinin through mutations in the Kelch13 protein. These mutations do not alter the protein's structure, but significantly affect its dynamics. Specifically, certain mutations lead to enhanced fluctuations in the BTB domain, which disrupts protein-protein interactions and contributes to drug resistance.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Immunology
Kai J. Rogers, Rahul Vijay, Noah S. Butler
Summary: Humoral immunity plays a critical role in limiting Plasmodium parasite infections and the severity of malaria. Naturally acquired immunity against malaria is inefficient and protection is relatively short-lived. Recent advances have been made in understanding the molecular and cellular pathways that regulate Plasmodium parasite-specific B cell responses and durable anti-malarial humoral immunity.
MICROBES AND INFECTION
(2021)
Article
Cell Biology
Angela D. Pack, Patrick Schwartzhoff, Zeb R. Zacharias, Daniel Fernandez-Ruiz, William R. Heath, Prajwal Gurung, Kevin L. Legge, Chris J. Janse, Noah S. Butler
Summary: During acute malaria, hemozoin deposition limits conventional dendritic cell function, resulting in aberrant T cell responses and impaired B cell and plasma cell formation, highlighting immune evasion mechanisms following initial Plasmodium exposure.
Article
Biochemistry & Molecular Biology
Pinar Siyah, Sezer Akgol, Serdar Durdagi, Fatih Kocabas
Summary: Plasmodium OTU-like proteins share highly conserved structures with viral OTU proteins and demonstrate Ubiquitin and ISG15 deconjugation activities. Through screening a library of small molecules, two potent inhibitors were identified with strong anti-malarial activity against P. falciparum, P. vivax, and P. yoelii OTU proteins.
BIOCHEMICAL JOURNAL
(2021)
Article
Microbiology
Nelson V. Simwela, W. Armand Guiguemde, Judith Straimer, Clement Regnault, Barbara H. Stokes, Luis E. Tavernelli, Fumiaki Yokokawa, Benjamin Taft, Thierry T. Diagana, Michael P. Barrett, Andrew P. Waters
Summary: This study used metabolomics technologies to characterize the potential targets of anti-malarial drug candidates and found that fast-acting leads induce a common biochemical theme in drug-exposed malaria parasites. These findings provide insights into the mode of action of fast drug candidates in future drug discovery programs.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biology
Hataichanok Chuljerm, Supawadee Maneekesorn, Voravuth Somsak, Yongmin Ma, Somdet Srichairatanakool, Pimpisid Koonyosying
Summary: The study demonstrated that the deferiprone-resveratrol hybrid exhibited a more potent inhibitory effect on malaria parasite growth, improved anemia and liver damage in infected mice, and had lower levels of lipid peroxidation products compared to deferiprone alone. The anti-malarial activity of the deferiprone-resveratrol hybrid was associated with anti-RBC hemolysis and liver weight index. Deferiprone-resveratrol hybrid showed anti-plasmodium, anti-hemolysis, and anti-lipid peroxidation activities more effectively than deferiprone in P. berghei-infected mice.
Review
Integrative & Complementary Medicine
Ye Xiong, Jianrong Huang
Summary: Artemisinin and its derivatives have been approved for the treatment of malaria and have shown anti-viral, anti-inflammatory, and anti-cancer effects. Studies suggest that they may protect the liver through multiple mechanisms, making them potential promising medicines for the treatment of liver diseases in the future.
Article
Biochemical Research Methods
Amber Kunkel, Michael White, Patrice Piola
Summary: Study aimed to understand impacts of triple ACTs and chemoprophylaxis in Cambodia using a mathematical model. Triple ACTs may limit spread of mefloquine resistance but have minimal impact on malaria incidence and could slow declines in piperaquine resistance. Chemoprophylaxis may reduce cases temporarily, but increases risks of resistance.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Chemistry, Physical
Phuong Thuy Viet Nguyen, Giang Le Tra Nguyen, Oanh Thi Dinh, Cuong Quoc Duong, Lam H. Nguyen, Thanh N. Truong
Summary: Selecting suitable drug targets is crucial in drug discovery. This study used a combination of druggability filtering, molecular docking, and molecular dynamics simulations to select suitable targets for dengue and malaria. The study identified druggable targets and performed molecular docking and MD simulations to evaluate their binding affinities. The results identified specific targets for further drug design studies.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Biochemistry & Molecular Biology
Prabhanshu Tripathi, Michael F. Bender, Haotian Lei, Lais Da Silva Pereira, Chen-Hsiang Shen, Brian Bonilla, Marlon Dillon, Li Ou, Marie Pancera, Lawrence T. Wang, Baoshan Zhang, Facundo D. Batista, Azza H. Idris, Robert A. Seder, Peter D. Kwong
Summary: The monoclonal antibody L9 recognizes the Plasmodium falciparum circumsporozoite protein and provides strong protection against malaria. Cryo-EM structures revealed that L9 recognizes PfCSP as an atypical trimer and interacts with a specific tetrapeptide on PfCSP to form the trimer. Both the epitope and homotypic components of L9 recognition are necessary for potent malaria protection, and the recognized peptide sequence is highly conserved in P. falciparum isolates, making it a promising vaccine target.
Review
Public, Environmental & Occupational Health
Aongart Mahittikorn, Wanida Mala, Polrat Wilairatana, Sukhontha Siri, Frederick Ramirez Masangkay, Kwuntida Uthaisar Kotepui, Manas Kotepui
Summary: This study conducted a systematic review and meta-analysis to characterize the prevalence, anti-malarial chemoprophylaxis, and causes of death for severe imported malaria. The results showed that the prevalence of severe imported malaria and deaths attributable to severe imported malaria was significant, while the prevalence of adequate anti-malarial chemoprophylaxis was low among patients with severe imported malaria. Multi-organ failure was identified as the most common cause of death. These findings emphasize the importance of education and preventative measures for individuals visiting malaria-endemic areas to minimize the risk of severe disease or death.
TRAVEL MEDICINE AND INFECTIOUS DISEASE
(2022)
Article
Pharmacology & Pharmacy
Jyoti Kumari, Vikash Kumar, Ankita Behl, Raj Kumar Sah, Geeta Kumari, Swati Garg, Aashima Gupta, S. Nazar Mohomed Mohaideen, Sadat Shafi, Soumya Pati, Kirandeep Samby, Jeremy Burrows, Narla Mohandas, Shailja Singh
Summary: The study shows that erythritol, a sugar substitute, has potential as a therapeutic intervention against drug-resistant malaria parasite Plasmodium falciparum. Erythritol effectively inhibits parasite growth and development, as well as invasion and egress processes. It also demonstrates inhibitory effects on liver stage and transmission stage parasites. In addition, erythritol has a cytokine-modulating effect and affects ammonia release across the parasite. The findings suggest that erythritol could be a promising lead compound for anti-malarial drugs and can be combined with existing drugs without losing efficacy.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Klaudia T. Angula, Lesetja J. Legoabe, Tarryn Swart, Heinrich C. Hoppe, Richard M. Beteck
Summary: Human African trypanosomiasis is a vector-borne tropical disease with potential global health and economic burdens. Novel quinolone derivatives show promising antitrypanosomal activity, making them a potential treatment option for the disease.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Omobolanle Janet Jesumoroti, Richard M. Beteck, Audrey Jordaan, Digby F. Warner, Lesetja J. Legoabe
Summary: Tuberculosis (TB) is a major cause of death worldwide. In this study, a library of 7H-Pyrrolo[2,3-d]pyrimidine derivatives was synthesized to develop new anti-TB compounds. Sixteen compounds showed activity against Mycobacterium tuberculosis, with the most potent derivative having a MIC90 value of 0.488 μM and no cytotoxicity. These findings suggest that these compounds have potential for further drug development and optimization.
MOLECULAR DIVERSITY
(2023)
Article
Chemistry, Medicinal
Richard M. Beteck, Michelle Isaacs, Lesetja J. Legoabe, Heinrich C. Hoppe, Christina C. Tam, Jong H. Kim, Jacobus P. Petzer, Luisa W. Cheng, Quincel Quiambao, Kirkwood M. Land, Setshaba D. Khanye
Summary: In this study, 21 novel small molecules inspired by metronidazole and Schiff base compounds were synthesized. These compounds showed potent inhibitory activity against Trichomonas vaginalis, as well as activity against Plasmodium falciparum and Trypanosomal brucei brucei. Compound 22 was a broad-spectrum antiprotozoal agent, exhibiting activity against all three pathogenic protozoans under investigation.
ARCHIV DER PHARMAZIE
(2023)
Article
Biochemistry & Molecular Biology
Charne du Preez, Lesetja J. Legoabe, Audrey Jordaan, Omobolanle J. Jesumoroti, Digby F. Warner, Richard M. Beteck
Summary: Curcumin, a natural product, exhibits antitubercular activity by inhibiting Mycobacterium tuberculosis and enhancing immune responses. However, it is unstable, and novel analogues like compound 3a have been synthesized and show potent antitubercular activity.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Article
Chemistry, Medicinal
Ogunyemi. O. O. Oderinlo, Audrey Jordaan, Ronnett Seldon, Michelle Isaacs, Heinrich. C. C. Hoppe, Digby. F. F. Warner, Matshawandile Tukulula, Setshaba. D. D. Khanye
Summary: An exploratory series of new triazole derivatives were synthesized by combining arylpyrrole and triazole units via a hydrazone linkage. Compound 13 showed reasonable activity against Mycobacterium tuberculosis, but other compounds in the series displayed weak antimycobacterial activity.
Review
Biochemistry & Molecular Biology
Phelelisiwe S. Dube, Lesetja J. Legoabe, Richard M. Beteck
Summary: The discovery of nalidixic acid in medicinal chemistry has had a profound impact, leading to the development of life-saving antimicrobial agents known as fluoroquinolones. However, the applications of quinolone compounds extend beyond fluoroquinolones, showing activity against various diseases such as malaria, tuberculosis, fungal and helminth infections. The versatility of the quinolone pharmacophore as a therapeutic agent is of great interest to researchers in diverse disciplines.
MOLECULAR DIVERSITY
(2023)
Article
Biochemistry & Molecular Biology
Koketso J. J. Setshedi, Richard M. M. Beteck, Omobolanle J. J. Jesumoroti, Kayhan Ilbeigi, Dorien Mabille, Guy Caljon, Frank Van der Kooy, Lesetja J. J. Legoabe
Summary: In this study, the synthesis of 2-aroyl quinazolinones and their antiprotozoal efficacy against Trypanosoma brucei, Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania infantum were reported. Thirteen out of the twenty target compounds inhibited the growth of these parasites, with compounds KJ1 and KJ10 exhibiting IC50 values of 4.7 μM (T. b. brucei) and 1.1 μM (T. b. rhodesiense), respectively.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Article
Biochemistry & Molecular Biology
Charles Arineitwe, Ogunyemi Oderinlo, Matshawandile Tukulula, Setshaba Khanye, Andile Khathi, Ntethelelo Sibiya
Summary: Diabetes mellitus (DM) and its complications have a significant impact on healthcare systems worldwide. In this study, four novel thiazolidinedione (TZD)-derivatives were synthesized and evaluated for their anti-diabetic properties. The derivatives showed strong binding to peroxisome proliferator-activated receptor-gamma (PPAR-gamma), similar to rosiglitazone. TZDD2 increased glucose uptake in liver cells compared to control. The derivatives exhibited inhibition activity in various enzymatic assays, including alpha-amylase, alpha-glucosidase, aldose reductase, and dipeptidyl peptidase-4.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Jessica Ramseier, Dennis Imhof, Kai Pascal Alexander Haenggeli, Nicoleta Anghel, Ghalia Boubaker, Richard M. Beteck, Luis-Miguel Ortega-Mora, Richard K. K. Haynes, Andrew Hemphill
Summary: The effects of decoquinate and three O-quinoline-carbamate-derivatives were investigated on human foreskin fibroblasts infected with Neospora caninum tachyzoites. These compounds exhibited different levels of proliferation inhibition and did not affect cell viability at certain concentrations. Treatment with lower concentrations altered the ultrastructure of the parasite, while long-term treatment with one compound showed parasiticidal effects. These compounds were then tested in a murine model, but did not show activity against neosporosis.
Article
Chemistry, Multidisciplinary
Phelelisiwe S. Dube, Klaudia T. Angula, Lesetja J. Legoabe, Audrey Jordaan, Jan M. Boitz Zarella, Digby F. Warner, J. Stone Doggett, Richard M. Beteck
Summary: In this study, 39 novel quinolone compounds with a hydrophilic amine chain and varied substituted benzyloxy units were described. These compounds demonstrated broad-spectrum activities against acid-fast bacterium, Gram-positive and-negative bacteria, fungi, and leishmania parasite. Compound 30 showed antitubercular activity against drug-resistant Mycobacterium tuberculosis, while compound 37 exhibited low micromolar activities against critical pathogens.
Article
Chemistry, Medicinal
Phelelisiwe S. Dube, Lesetja J. Legoabe, Audrey Jordaan, Lester Sigauke, Digby F. Warner, Richard M. Beteck
Summary: Mycobacterium tuberculosis (Mtb) has an impermeable cell wall, making it resistant to many antibiotics. DprE1 is a crucial enzyme in Mtb cell wall synthesis, and has been identified as a target for potential tuberculosis drugs. PBTZ169 is the most promising DprE1 inhibitor, but more drug candidates are needed. By modifying the structure of PBTZ169, we synthesized 22 compounds and found that six of them exhibited sub-micromolar activity against Mtb. Compound 25 showed sub-micromolar activity against wild-type and fluoroquinolone-resistant Mtb strains.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Devesh S. Agarwal, Rajeev Sakhuja, Richard M. Beteck, Lesetja J. Legoabe
Summary: Steroids are biomolecules that play important roles in physiology and drug discovery. Research on steroid-heterocycle conjugates as potential therapeutic agents, especially anticancer agents, has increased over the past few decades. This review summarizes the synthesis, anticancer activity, and structure-activity relationship (SAR) of various steroid-triazole conjugates against different cancer cell lines. It provides a foundation for the development of steroid-heterocycle conjugates with reduced side effects and improved efficacy.
Article
Biochemistry & Molecular Biology
Devesh S. Agarwal, Richard M. Beteck, Kayhan Ilbeigi, Guy Caljon, Lesetja J. Legoabe
Summary: A library of imidazo[1,2-a]pyridine-appended chalcones were synthesized and characterized. These compounds exhibited significant antikinetoplastid activity against Trypanosoma cruzi and Trypanosoma brucei brucei, and non-cytotoxicity against normal cells.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Article
Chemistry, Multidisciplinary
Siya T. Hulushe, Frederick P. Malan, Eric C. Hosten, Kevin A. Lobb, Setshaba D. Khanye, Gareth M. Watkins
Summary: This study presents the mechanochemical synthesis of photo- and thermoresponsive N-Salicylideneaniline derivatives and investigates their solid-state stabilization through temperature variation and photoirradiation. It demonstrates the influence of UV light on proton transfer between different tautomeric forms and provides insights into the thermomechanical behavior and thermochromaticity. The importance of applying complementary analytical techniques for understanding the switching behavior between different forms is emphasized.
NEW JOURNAL OF CHEMISTRY
(2022)
