A5056277710- Cancer therapeutics and mechanisms
- Tuberculosis Research and Epidemiology
- Synthesis and biological activity
- Synthesis and Biological Evaluation
- Phenothiazines and Benzothiazines Synthesis and Activities
- HIV/AIDS drug development and treatment
- Antibiotic Resistance in Bacteria
- Biochemical and Molecular Research
- Click Chemistry and Applications
- Quinazolinone synthesis and applications
- Research on Leishmaniasis Studies
- Essential Oils and Antimicrobial Activity
- Natural product bioactivities and synthesis
- Multicomponent Synthesis of Heterocycles
- Trypanosoma species research and implications
- X-ray Diffraction in Crystallography
- Metal complexes synthesis and properties
- Crystallization and Solubility Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Mycobacterium research and diagnosis
- Bioactive Compounds and Antitumor Agents
- Natural Antidiabetic Agents Studies
- Curcumin's Biomedical Applications
- Eicosanoids and Hypertension Pharmacology
- Biological Activity of Diterpenoids and Biflavonoids
University of Cape Town
2019-2024
South African Medical Research Council
2019-2024
Two libraries of quinoline-based hybrids 1-(7-chloroquinolin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine and 7-chloro-N-phenylquinolin-4-amine were synthesized evaluated for their α-glucosidase inhibitory antioxidant properties. Compounds with 4-methylpiperidine para-trifluoromethoxy groups, respectively, showed the most promising inhibition activity IC
Herein, we propose novel quinolones incorporating an INH moiety as potential drug templates against TB. The quinolone-based compounds bearing attached via a hydrazide-hydrazone bond were synthesised and evaluated Mycobacterium tuberculosis H37Rv (MTB). also for cytotoxicity HeLa cell lines. These showed significant activity (MIC90) MTB in the range of 0.2-8 μM without any cytotoxic effects. Compounds 10 (MIC90; 0.9 μM), 11 0.2 12 0.8 μM) compound 15 most active this series, demonstrate...
Mycobacterium tuberculosis , the causative agent of tuberculosis, remains a leading infectious killer globally, demanding urgent development faster-acting drugs with novel mechanisms action. Riminophenazines such as clofazimine are clinically efficacious against both drug-susceptible and drug-resistant strains M. .
Co-infection of malaria and tuberculosis, although not thoroughly investigated, has been noted. With the increasing prevalence tuberculosis in African region, wherein is endemic, it intuitive to suggest that probability co-infection with these diseases likely increase. To avoid issue drug-drug interactions when managing co-infections, imperative investigate new molecules dual activities against causal agents diseases. this effect, a small library quinolone-thiosemicarbazones was synthesised...
Tuberculosis is the deadliest infectious disease affecting humankind with a death toll of approximately 1.7 million people in 2016. The increasing prevalence multidrug-resistant strains causative pathogen, Mycobacterium tuberculosis (Mtb) which results reduced effectiveness current therapies, underscores urgent need for development new antitubercular drugs. In search such drugs, we investigated two series ciprofloxacin (CPX) derivatives (analogues and hybrids). We herein report design,...
Herein, we describe 39 novel quinolone compounds bearing a hydrophilic amine chain and varied substituted benzyloxy units. These demonstrate broad-spectrum activities against acid-fast bacterium, Gram-positive -negative bacteria, fungi, leishmania parasite. Compound 30 maintained antitubercular activity moxifloxacin-, isoniazid-, rifampicin-resistant Mycobacterium tuberculosis, while 37 exhibited low micromolar (<1 μg/mL) World Health Organization (WHO) critical pathogens: Cryptococcus...
Mycobacterium tuberculosis (Mtb) has an impermeable cell wall which gives it inherent ability to resist many antibiotics. DprE1, essential enzyme in Mtb synthesis, been validated as a target for several TB drug candidates. The most potent and developmentally advanced DprE1 inhibitor, PBTZ169, is still undergoing clinical development. With high attrition rate, there need populate the development pipeline. Using scaffold hopping strategy, we imprinted benzenoid ring of PBTZ169 onto quinolone...
Medicinal plants of the Plectranthus genus (Lamiaceae) are well known for their ethnomedicinal applications. madagascariensis, which is native to South Africa, traditionally used in treatment respiratory conditions, scabies, and cutaneous wounds. The phytochemical studies P. madagascariensis led isolation five royleanone abietanes, namely, 6β,7α-dihydroxyroyleanone (1), 7α-acetoxy-6β-hydroxyroyleanone (2), horminone (3), coleon U quinone (4), carnosolon (5). relative configuration compound 2...
Nitrothiazole derivatives have been reported to exhibit activity against aerobic, anaerobic, and microaerophilic bacteria. This profile makes the nitrothiazole compound class an ideal lead source Mycobacterium tuberculosis, which flourishes in varied environments with different oxygen concentrations. In this work, we investigated six for antitubercular activity. The compounds exhibited potent activity, 9 10 possessing equipotent MIC90 value of 0.24 µM. were cytotoxicity HEK293 cells...
The cell wall of Mycobacterium tuberculosis (Mtb) has a unique structural organisation, comprising high lipid content mixed with polysaccharides. This makes formidable barrier impermeable to hydrophilic agents. In addition, during host infection, Mtb resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from action most antibiotics. To overcome these protective barriers, new class anti-TB agents exhibiting lipophilic character have been...
Compounds containing arylpyrrole-, 1,2,4-triazole- and hydrazone structural frameworks have been widely studied demonstrated to exhibit a wide range of pharmacological properties. Herein, an exploratory series new 1,2,4-triazole derivatives designed by amalgamation arylpyrrole units via linkage is reported. The synthesised compounds were tested in vitro for their potential activity against Mycobacterium tuberculosis (MTB) H37 Rv strain. most promising compound 13 - the derivative without...
While N-acetyl azaaurones have already been disclosed for their potential against tuberculosis (TB), low metabolic stability remains an unaddressed liability. We now report a study designed to improve the and solubility of azaaurone scaffold identify structural requirements antimycobacterial activity. Replacing moiety N-carbamoyl group led analogues with sub- nanomolar potencies M. H37Rv, as well equipotent drug-susceptible drug-resistant isolates. The new exhibited improved microsomal...
Curcumin is a natural product that has been reported to exhibit myriad pharmacological properties, one of which antitubercular activity. It demonstrates activity by directly inhibiting Mycobacterium tuberculosis (M.tb) and also enhances immune responses ultimately lead the elimination M.tb macrophages. This is, however, unstable, several analogues, noticeably monocarbonyl have synthesized overcome this challenge. its analogues so far moderate in range 7 16 μM. Herein, we report...
In this study, we synthesized novel nitro quinolone-based compounds and tested them in vitro against a panel of Gram-positive Gram-negative pathogens including Mycobacterium tuberculosis (MTB), Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumonia, Staphylococcus aureus, Escherichia coli for antibacterial activities also HeLa cells overt cytotoxicity. Compound 8e was identified as non-toxic, potent hit with selective activity (MIC90 ˂ 0.24 µm) MTB. 8e, however, showed no...
Compounds with novel modes of action are urgently needed to develop effective combination therapies for the treatment tuberculosis. In this study, a series compounds was evaluated activity against replicating Mycobacterium tuberculosis and Vero cell line toxicity. Fourteen in vitro activities low micrometer range favorable selectivity index were classified using reporter strains M. which showed that six interfered wall metabolism one disrupted DNA metabolism. Counter-screening carrying...
Mycobacterium tuberculosis has developed extensive resistance to numerous antimycobacterial agents used in the treatment of tuberculosis. Insufficient intracellular accumulation active moieties allows for selective survival mycobacteria with drug mutations and accordingly promotes development microbial resistance. Discovery compounds new mechanisms action physicochemical properties that promote accumulation, or act synergistically other drugs, potential reduce prevent further To this end,...