Review
Chemistry, Multidisciplinary
Pitambar Khanal
Summary: Artesunate and other artemisinins are effective antimalarial drugs, with artesunate showing superiority in treating severe malaria compared to other artemisinins. Additionally, they have the potential to be developed as anticancer drugs.
MONATSHEFTE FUR CHEMIE
(2021)
Review
Biochemistry & Molecular Biology
Tereza Kauerova, Maria-Jesus Perez-Perez, Peter Kollar
Summary: Salicylanilides are pharmacologically active compounds with a wide spectrum of biological effects. Recent studies have shown that halogenated salicylanilides, including the well-studied niclosamide, have potential anticancer properties mediated by various mechanisms such as uncoupling oxidative phosphorylation and inhibiting protein tyrosine kinase. This article provides a comprehensive overview of the proposed mechanisms and structural requirements for the anticancer activity of salicylanilides based on preclinical studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Medicinal
Zi-wei Zeng, Di Chen, Lei Chen, Bin He, Yan Li
Summary: Artemisinin, an important ingredient of artemisia annua, has been traditionally used for malaria therapy in China for hundreds of years. Recent research has also revealed the anticancer properties of artemisinin and its derivatives. This review summarizes the development of artemisinin and its derivatives as anticancer agents, including natural and synthetic monomers as well as their dimers. It also discusses the mechanisms of action and clinical trials of artemisinin-based drugs for cancer treatment, providing valuable insights for the development of novel anticancer drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ratchanok Pingaew, Prasit Mandi, Veda Prachayasittikul, Anusit Thongnum, Supaluk Prachayasittikul, Somsak Ruchirawat, Virapong Prachayasittikul
Summary: The study found that hydroxyl-containing bisindoles exhibited good anticancer activity against multiple cancer cell lines, with some derivatives also showing antimalarial effects, while non-hydroxyl-containing bisindoles were more suitable as antimalarial agents. Five QSAR models were constructed to guide the design and synthesis of an additional set of 22 compounds. Molecular docking revealed the binding modes between the compounds and target proteins.
Article
Chemistry, Inorganic & Nuclear
Chun Hau Gan, Kong Wai Tan, Mei Lee Ooi, Jonathan Wee Kent Liew, Yee Ling Ng, Yee Ling Lau, Yin Zhuang Ng, Chew Hee Ng, Chun Hoe Tan, Richard C. S. Wong
Summary: The article investigated the synthesis, structural characterization, and potential applications of different metal complexes in photoCORMs, anticancer, and antimalarial activities. In vitro cell studies showed significant cytotoxic effects of these compounds on specific sub-types of breast cancer cells.
INORGANICA CHIMICA ACTA
(2022)
Review
Medicine, Research & Experimental
Omar Belmehdi, Douae Taha, Jamal Abrini, Long Chiau Ming, Asaad Khalid, Ashraf N. Abdalla, Alanood S. Algarni, Andi Hermansyah, Abdelhakim Bouyahya
Summary: α-Hederin is a natural bioactive molecule abundant in aromatic and medicinal plants, with potential anticancer activity. Its mechanisms of action include inducing apoptosis and cell cycle arrest, reducing ATP generation, and inhibiting autophagy, cell proliferation, invasion, and metastasis. These anticancer mechanisms make it a promising candidate for chemotherapy, either alone or in combination with other validated or investigational molecules that sensitize tumor cells to chemotherapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Mahsa Shahriari, Prashant Kesharwani, Thomas P. Johnston, Amirhossein Sahebkar
Summary: Cancer is a widespread disease with various treatment modalities and challenges. Chemotherapy has limitations due to toxicity and drug resistance. Curcumin, a natural compound with multiple therapeutic properties, has poor solubility and limited bioavailability. Cyclodextrin complexes of curcumin improve its properties, and beta-cyclodextrin is commonly used. This review focuses on comparing different curcumin-cyclodextrin formulations.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Microbiology
Silvia Parapini, Silvio Paone, Emanuela Erba, Loredana Cavicchini, Manoochehr Pourshaban, Francesco Celani, Alessandro Contini, Sarah D'Alessandro, Anna Olivieri
Summary: Malaria causes numerous cases and deaths annually, and the search for novel antimalarial drugs is essential. This study tested a series of Rac1 inhibitors and found that EHop-016 exhibited the most effective inhibitory activity against Plasmodium falciparum, without affecting red blood cell invasion but impacting parasite growth internally.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Chemistry, Medicinal
Tim Van de Walle, Lore Cools, Sven Mangelinckx, Matthias D'hooghe
Summary: Quinoline, a privileged scaffold in medicinal chemistry, plays a central role in antimalarial and anticancer research, but established quinoline-containing antimalarial drugs are facing widespread resistance. On the other hand, there is a growing interest in quinoline compounds as potential anticancer agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Applied
Laura Gallego-Yerga, Cristina de la Torre, Francesco Sansone, Alessandro Casnati, Carmen Ortiz Mellet, Jose M. Garcia Fernandez, Valentin Cena
Summary: Cyclodextrin-calixarene giant amphiphiles are capable of encapsulating and delivering anticancer drugs to tumor cells with high efficiency, significantly enhancing therapeutic efficacy. The redox-responsive disulfide bridge modification in these amphiphiles allows for efficient cargo release in a tumor microenvironment, leading to potent inhibition of cancer cell proliferation.
CARBOHYDRATE POLYMERS
(2021)
Article
Multidisciplinary Sciences
Tanyaluck Kampoun, Pimpisid Koonyosying, Jetsada Ruangsuriya, Parichat Prommana, Philip J. Shaw, Sumalee Kamchonwongpaisan, Hery Suwito, Ni Nyoman Tri Puspaningsih, Chairat Uthaipibull, Somdet Srichairatanakool
Summary: This study found that the antimalarial compound C3 and iron chelators have similar antimalarial effects and inhibit the action of iron ions on dihydroartemisinin (DHA). The results suggest that drugs with inhibitory effects on the Fd/FNR redox system should be avoided as partner drugs for DHA in combination therapy.
Article
Dentistry, Oral Surgery & Medicine
J. T. Marchesan, K. Moss, T. Morelli, F. R. Teles, K. Divaris, M. Styner, A. A. Ribeiro, J. Webster-Cyriaque, J. Beck
Summary: This study analyzed data from 1,450 adult participants in the ARIC study and found that men and African Americans had higher systemic antibody levels against most microorganisms, while healthy individuals had low levels of biofilm bacteria and serum IgG levels. Additionally, individuals in different PPC classifications showed distinct microbial profiles.
JOURNAL OF DENTAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Katarzyna Krancewicz, Karolina Nowicka-Bauer, Katarzyna Fiedorowicz, Bronislaw Marciniak, Katarzyna Taras-Goslinska
Summary: In this study, a group of guanosine analogues containing an additional five-membered ring and a sulfur atom at the C-9 position were synthesized. The spectral, photophysical, and biological properties of the synthesized compounds were investigated. It was found that the combination of the thiocarbonyl chromophore and the tricyclic structure of guanine analogues allows for selective excitation above 350 nm, showing promising potential as anticancer agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Raghad Al-Jarf, Alex G. C. de Sa, Douglas E. Pires, David B. Ascher
Summary: The development of a novel predictive tool, pdCSM-cancer, provides an accurate way to predict molecules likely to be active against one or multiple cancer cell lines by using graph-based chemical structure signatures. This tool includes trained and validated models on data from over 18,000 compounds on 9 tumor types and 74 distinct cancer cell lines, achieving successful predictive performance.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Review
Pharmacology & Pharmacy
Yihui Song, Xiaoke Yang, Bin Yu
Summary: Drug repurposing is an attractive strategy for finding new indications for existing drugs. Three approved antidepressants have shown potential in clinical trials for cancer treatment. By conducting further medicinal chemistry research, several TCP-based inhibitors of the histone lysine specific demethylase 1 enzyme have been discovered, showing promise for cancer treatment. Repurposing antidepressants could be a promising strategy for cancer treatment.
DRUG DISCOVERY TODAY
(2022)
Article
Chemistry, Multidisciplinary
Monalisa Roy, Keyao Li, Madiha Nisar, Lawrence W-Y Wong, Herman H-Y Sung, Richard K. Haynes, Ian D. Williams
Summary: The X-ray structures of three new 1:1 pharmaceutical cocrystals of 11-aza-artemisinin with bromo-substituted salicylic acids are reported, showing variations in their packing arrangements. This study provides insight into the crystal packing efficiency of the cocrystals based on hydrogen bonding interactions.
ACTA CRYSTALLOGRAPHICA SECTION C-STRUCTURAL CHEMISTRY
(2021)
Article
Microbiology
Daniel J. Watson, Lizahn Laing, Liezl Gibhard, Ho Ning Wong, Richard K. Haynes, Lubbe Wiesner
Summary: The article reviews the pharmacokinetic properties of various amino-artemisinins in mice, highlighting their potential as components of triple combination therapies due to favorable efficacy and pharmacokinetics.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Microbiology
Francesca Sisto, Simone Carradori, Sarah D'Alessandro, Nadia Santo, Norma Lattuada, Richard K. Haynes, Donatella Taramelli, Rossella Grande
Summary: This study evaluated the in vitro activity of arylaminoartemisinin GC012 against clinical strains of H. pylori with different antibiotic susceptibilities. GC012 showed significantly lower MIC and MBC values compared to DHA, indicating its potential as an effective treatment for H. pylori infection. Combination of GC012 with metronidazole, clarithromycin, and amoxicillin displayed synergistic interactions. Additionally, GC012 inhibited biofilm formation and showed minimal biofilm eradication concentration (MBEC) on mature biofilm. Structural changes in the bacterial membrane were observed for both GC012 and DHA.
Review
Infectious Diseases
Danielle van Staden, Richard K. Haynes, Joe M. Viljoen
Summary: Despite available chemotherapeutic treatment regimens and efforts to develop new drugs for tuberculosis, the disease remains challenging to treat due to the nature of the causative pathogen and drug resistance. The World Health Organization introduced the End-TB initiative to eliminate tuberculosis, but the COVID-19 pandemic has hindered progress. Therefore, there is a need for enhanced scientific understanding, repurposing of drugs, and new treatment methods. This review focuses on utilizing self-double-emulsifying drug delivery systems for topical treatment of cutaneous tuberculosis and other mycobacterial infections.
Article
Pharmacology & Pharmacy
Daniel J. J. Watson, Lizahn Laing, Richard M. M. Beteck, Liezl Gibhard, Richard K. K. Haynes, Lubbe Wiesner
Summary: The emergence of drug-resistant malaria strains has necessitated the development of new combination therapies. In this study, the pharmacokinetics of decoquinate and its derivatives were analyzed, revealing promising activity and ease of preparation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jerome P. L. Ng, Yu Han, Li Jun Yang, Lyn-Marie Birkholtz, Dina Coertzen, Ho Ning Wong, Richard K. Haynes, Paolo Coghi, Vincent Kam Wai Wong
Summary: Artemisinin, a compound derived from the traditional Chinese medicinal plant Artemisia annua, is commonly used for malaria treatment. However, the emergence of drug resistance has prompted the search for new drug combinations. This study found that the triterpenoid quinone methide celastrol, isolated from the traditional Chinese medicinal plant Tripterygium wilfordii, displayed good antimalarial activity in combination with amino-artemisinins. Celastrol also showed synergistic effects against liver cancer cells. However, further modifications are needed to mitigate its toxicity.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Crystallography
Keyao Li, Monalisa Roy, Madiha Nisar, Lawrence W-Y Wong, Herman H-Y Sung, Richard K. Haynes, Ian D. Williams
Summary: This study demonstrates the formation of different types of cocrystals using different seeds, while also showing the role of halogen bonds in discriminating between different polymorphic types.
Article
Pharmacology & Pharmacy
J. W. Bezuidenhout, M. Aucamp, N. Stieger, W. Liebenberg, R. K. Haynes
Summary: To establish the best processing parameters and storage conditions for nanolipid formulations of artesunate, the thermal stability and solubility profiles of artesunate in aqueous solutions were evaluated at different temperatures and pH levels. The study found that artesunate remained relatively stable at temperatures up to 40°C and 75% relative humidity for 3 months, with approximately 9% decomposition. However, higher temperatures led to significantly greater decomposition and the formation of dihydroartemisinin (DHA) and other products. The solubility of artesunate varied with pH, with the highest solubility observed at pH 6.8 (phosphate buffer). Overall, maintaining relatively low temperatures is crucial for the preparation and storage of artesunate formulations.
Article
Biochemistry & Molecular Biology
Giovanni Ribaudo, Xiaoyun Yun, Alberto Ongaro, Erika Oselladore, Jerome P. L. Ng, Richard K. Haynes, Betty Yuen Kwan Law, Maurizio Memo, Vincent Kam Wai Wong, Paolo Coghi, Alessandra Gianoncelli
Summary: By utilizing computational tools, this study identified two potential antimalarial drugs, amodiaquine and methylene blue, as possible PLpro inhibitors. These findings provide a starting point for the development of new PLpro inhibitors.
CHEMICAL BIOLOGY & DRUG DESIGN
(2023)
Review
Plant Sciences
Barend Jacobus Lee, Morne Weyers, Richard Kingston Haynes, Frank van der Kooy
Summary: This article reviews the history of the discovery of artemisinin and the development of combination therapies, as well as the current production techniques and the possibility of producing artemisinin in South Africa. Although artemisinin and its derivatives are widely used for malaria treatment worldwide, the supply is insufficient, especially when used for other diseases. To meet the demand, higher yielding cultivars and novel extraction and purification techniques are needed.
SOUTH AFRICAN JOURNAL OF BOTANY
(2023)
Article
Parasitology
Joachim Mueller, Carling Schlange, Manfred Heller, Anne-Christine Uldry, Sophie Braga-Lagache, Richard K. Haynes, Andrew Hemphill
Summary: Artemisinin and its amino-artemisinin derivatives are potent antimalarials and exhibit different mechanisms of action against Plasmodium and T. gondii. The amino-artemisinins are effective in vitro against non-heme-degrading apicomplexan parasites including T. gondii. However, T. gondii strains readily adapt to increased concentrations of these compounds, resulting in the development of resistant strains.
INTERNATIONAL JOURNAL FOR PARASITOLOGY-DRUGS AND DRUG RESISTANCE
(2023)
Review
Pharmacology & Pharmacy
Danielle van Staden, Richard K. K. Haynes, Joe M. M. Viljoen
Summary: Self-emulsification is a formulation technique that improves oral drug delivery by enhancing solubility and bioavailability. It provides a simplified method for delivering lipophilic drugs by producing emulsions upon moderate agitation and dilution. It is also a promising approach for topical drug delivery, offering simplified production procedures and unlimited upscaling possibilities.
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, Medicinal
Danielle van Staden, Richard K. Haynes, Joe M. Viljoen
Summary: Self-emulsifying drug delivery systems (SEDDSs) are lipid-based systems that provide superior drug protection and control over drug concentration profiles, making them a promising option for oral drug delivery. Dermal spontaneous emulsions have also gained interest due to their ability to deliver drugs across mucus membranes and skin layers.
Review
Chemistry, Medicinal
Lorencia Taljaard, Richard K. Haynes, Frank van der Kooy
Summary: Schistosomiasis, a neglected tropical disease, can be controlled and ultimately eliminated by reducing snail populations and preventing and treating schistosomiasis infections. Novel antischistosomal drugs are needed to address concerns about drug resistance, and the genus Artemisia shows promise due to its effects on both schistosomes and snail vectors. The combination of artemisinin and praziquantel presents a potential treatment option for schistosomiasis.
REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY
(2023)