A5076808812- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Ferrocene Chemistry and Applications
- Synthesis and Biological Evaluation
- Metal complexes synthesis and properties
- Malaria Research and Control
- Synthesis and biological activity
- Crystallography and molecular interactions
- HIV/AIDS drug development and treatment
- Hearing, Cochlea, Tinnitus, Genetics
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Connexins and lens biology
- Peptidase Inhibition and Analysis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Reactivity of Heterocycles
- Natural product bioactivities and synthesis
- Traditional and Medicinal Uses of Annonaceae
- Cancer therapeutics and mechanisms
- Cancer-related molecular mechanisms research
- Synthesis and Characterization of Heterocyclic Compounds
- Tuberculosis Research and Epidemiology
- Organometallic Compounds Synthesis and Characterization
- Hearing Loss and Rehabilitation
- Quinazolinone synthesis and applications
University of Cape Town
2015-2025
Groote Schuur Hospital
2012-2018
National Observatory
2015-2016
Rhodes University
2015
The 2-aminopyridine MMV048 was the first drug candidate inhibiting Plasmodium phosphatidylinositol 4-kinase (PI4K), a novel target for malaria, to enter clinical development. In an effort identify next generation of PI4K inhibitors, series optimized improve properties such as solubility and antiplasmodial potency across parasite life cycle, leading 2-aminopyrazine UCT943.
For the treatment of malaria which affects nearly 200 million people each year and continued exacerbation by emergence drug resistance to most available antimalarials, "covalent bitherapy" suggests hybrid molecules be next-generation antimalarial drugs. In this investigation, new hybrids 4-aminoquinoline pyrimidine moieties that show antiplasmodial activity in nM range against chloroquine-resistant as well chloroquine-sensitive strains Plasmodium falciparum have been prepared. Cytotoxicity...
A series of aryl-functionalized and ferrocenyl monothiosemicarbazone compounds (L1–L4) were synthesized in moderate yields via a general Schiff-base condensation reaction. The thiosemicarbazone (TSC) ligands reacted with the ruthenium dimer [Ru(Ar)(μ-Cl)Cl]2 (Ar = benzene; p-cymene) to yield cationic mononuclear ruthenium(II)–arene complexes type [Ru(Cl)(TSC)(Ar)]Cl (1–8). act as bidentate chelating that coordinate ruthenium(II) ion imine nitrogen thione sulfur atoms. ligands, well their...
Tridentate cycloplatinated thiosemicarbazone complexes have been prepared from a biologically significant ligand, 3,4-dichloroacetophenone (1). The tetranuclear complex 2 was by reaction of the ligand with K2[PtCl4]. Two mononuclear (3 and 4) two dinuclear (5 6) were isolated upon cleavage Pt–Sbridging bonds appropriate phosphane ligand. Each characterized using various analytical spectroscopic techniques, molecular structures 2–4 also elucidated. in vitro antiparasitic activities these...
High-throughput screening of a library small polar molecules against Mycobacterium tuberculosis led to the identification phthalimide-containing ester hit compound (1), which was optimized for metabolic stability by replacing moiety with methyl oxadiazole bioisostere. A route utilizing polymer-supported reagents designed and executed explore structure-activity relationships respect N-benzyl substituent, leading compounds nanomolar activity. The frontrunner (5h) from these studies well...
Five compounds displaying an unprecedented binding mode of chloroquine to ferrocene through the bridging cyclopentadienyl rings were studied alongside their monosubstituted analogues and organic fragments. The antiplasmodial activity was evaluated against strains malaria parasite (Plasmodium falciparum). While chloroquine-bridged ferrocenyl derivatives less active than five analogues, they retained in drug-resistant strains. biological physical properties correlated activity. Intramolecular...
Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH), a key enzyme in the de novo pyrimidine biosynthesis pathway, which relies on exclusively for survival, has emerged as promising target antimalarial drugs. In an effort to discover new and potent PfDHODH inhibitors, 3D-QSAR pharmacophore models were developed based structures of known inhibitors validated Hypo1 model was used 3D search query virtual screening National Cancer Institute database. The hit compounds further filtered...
Thirteen new ruthenium and osmium half-sandwich complexes with chloroquine analogue ligands have been synthesized evaluated for anti-malarial properties.
Ferrocenyl- and aryl-functionalised organosilane thiosemicarbazones.
Two silicon-containing analogues (1, 2) of chloroquine, modified in the lateral side chain with organosilicon moieties, were synthesized. Compounds 1 and 2 further reacted dinuclear half-sandwich transition metal precursors [Ru(Ar)(μ-Cl)Cl]2 (Ar = η6-p-iPrC6H4Me; η6-C6H6; η6-C6H5OCH2CH2OH), [Rh(COD)(μ-Cl)]2, [RhCp*(μ-Cl)Cl]2, to yield a series neutral mononuclear Ru(II), Rh(I), Rh(III) silicon-aminoquinoline complexes (3–12). act as monodentate donors that coordinate metals via quinoline...
Organometallic analogues of chloroquine show promise as new antimalarial agents capable overcoming resistance to the parent drug chloroquine. Here, synthesis and characterization three cymantrene (CpMn(CO)3) cyrhetrene (CpRe(CO)3) 4-aminoquinoline conjugates with either an amine or amide linker are reported. The activity organometallic N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cymantrenylbutanamide (3), N-(2-(7-chloroquinolin-4-ylamino)ethyl)-4-cyrhetrenylbutanamide (4)...
A silicon-containing congener of ferroquine (1) was synthesized by incorporating an organosilicon motif in the lateral side chain ferroquine. Compound 1 then further reacted with dinuclear half-sandwich transition-metal precursors [Ru(Ar)(μ-Cl)Cl]2 (Ar = η6-p-iPrC6H4Me, η6-C6H6, η6-C6H5OCH2CH2OH), [Rh(COD)(μ-Cl)]2, and [RhCp*(μ-Cl)Cl]2, to yield a series heterometallic organometallic complexes (2–6). coordinates selectively monodentate manner transition metals via quinoline nitrogen...
Our study aimed to investigate GJB2 (connexin 26) and GJB6 30) mutations associated with non-syndromic childhood hearing impairment (HI) as well the environmental causes of HI in Ghana. Medical reports 1,104 students attending schools for deaf were analyzed. Families segregating HI, isolated cases putative genetic origin recruited. DNA was extracted from peripheral blood followed by Sanger sequencing entire coding region GJB2. Multiplex PCR used analyze prevalence GJB6-D3S1830 deletion....
A novel series of 2,4-diaminothienopyrimidines with potential as antimalarials was identified from whole-cell high-throughput screening a SoftFocus ion channel library. Synthesis and structure-activity relationship studies compounds potent antiplasmodial activity low in vitro cytotoxicity. Several these analogues exhibited vivo the Plasmodium berghei mouse model when administered orally. However, inhibition hERG potassium liability for this series.
Background: Over three-quarters of the people living with hearing impairment (HI) live in low- and middle-income countries. However, Rwanda has limited data on clinical profile HI. Aim: We used community-based nationwide recruitment participants to determine etiology early-onset (<7 years age) HI Rwanda. Methods: Participants were included after examination, including audiological assessment by pure tone audiometry and/or auditory brainstem response. DNA was extracted from peripheral...
ABSTRACT To elucidate the genetic etiology of hearing impairment (HI) in South Africa, 45 nonsyndromic HI (NSHI) and syndromic (SHI) families with ≥ 2 affected members were analyzed. Exome sanger sequencing used to identify causal genes. For NSHI, 14 24 segregated variants NSHI genes, that is, CDH23 , GJB2 MITF MYO7A, MYO15A PCDH15 POU3F4 REST SLC26A4 TMPRSS3 WFS1 . 21 SHI families, have Waardenburg syndrome, two Branchio‐Oto‐Renal syndromes, one each Bartter, Chudley‐McCullough,...
This work presents a new class of organometallic antimalarials, based on ferrocene scaffold, bearing chloroquine derivative and 1,2;3,5-(diisopropylidene)-α-d-glucofuranose moiety in 1,1′-heteroannular substitution pattern. Synthesis proceeds via orthogonal functionalization ferrocene, giving 1-acetoxy-1′-(1,3-dioxan-2-yl)ferrocene (15) as the precursor for modular introduction carbohydrate (16, 17) followed by subsequent reductive amination with building blocks 8–10, yielding...