Research Articles (School of Pharmacy)

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3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (σ1) receptor
(Elsevier, 2013) Geldenhuys, Werner J.; Novotny, Nicholas; Malan, Sarel F.; Van der Schyf, Cornelis J.
Pentacycloundecylamine (PCU) derived compounds have been shown to be promising lead structures for the development of novel drug candidates aimed at a variety of neurodegenerative and psychiatric diseases. Here we show for the first time a 3D quantitative structure–activity relationship (3D-QSAR) for a series of aza-PCU-derived compounds with activity at the sigma-1 (r1) receptor. A comparative molecular field analysis (CoMFA) model was developed with a partial least squares cross validated (q2) regression value of 0.6, and a non-cross validatedr2 of 0.9. The CoMFA model was effective at predicting the sigma-1 activities of atest set with an r2 >0.7. We also describe here the docking of the PCU-derivedcompounds into a homology model of the sigma-1 (r1) receptor, which was developed to gain insight into binding of these cage compounds to the receptor. Based on docking studies we evaluated in a [3H]pentazocine binding assay anoxa-PCU, NGP1-01 (IC50 = 1.78 lM) and its phenethyl derivative (IC50 = 1.54 lM). Results from these studies can be used to develop new compounds with specific affinity for the sigma-1(r1)
4-oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives as nmda receptor- And VGCC blockers with neuroprotective potential
(MPDI, 2020) Egunlusi, Ayodeji O.; Malan, Sarel F.; Omoruyi, Sylvester Ifeanyi
The impact of excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptor overactivation and voltage gated calcium channel (VGCC) depolarization is prominent among the postulated processes involved in the development of neurodegenerative disorders. NGP1-01, a polycyclic amine, has been shown to be neuroprotective through modulation of the NMDA receptor and VGCC, and attenuation of MPP+-induced neurotoxicity. Recently, we reported on the calcium modulating effects of tricycloundecene derivatives, structurally similar to NGP1-01, on the NMDA receptor and VGCC of synaptoneurosomes. In the present study, we investigated novel 4-oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives for their cytotoxicity, neuroprotective effects via attenuation of MPP+-induced neurotoxicity and calcium influx inhibition abilities through the NMDA receptor and VGCC using neuroblastoma SH-SY5Y cells. All compounds, in general, showed low or no toxicity against neuroblastoma cells at 10-50 μM concentrations. At 10 μM, all compounds significantly attenuated MPP+-induced neurotoxicity as evident by the enhancement in cell viability between 23.05 ± 3.45% to 53.56 ± 9.29%.
4-Oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione Derivatives as NMDA Receptor- and VGCC Blockers with Neuroprotective Potential
(MDPI, 2020) Egunlusi, A; Malan, S; Omoruyi, S
The impact of excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptor overactivation and voltage gated calcium channel (VGCC) depolarization is prominent among the postulated processes involved in the development of neurodegenerative disorders. NGP1-01, a polycyclic amine, has been shown to be neuroprotective through modulation of the NMDA receptor and VGCC, and attenuation of MPP+-induced neurotoxicity. Recently, we reported on the calcium modulating effects of tricycloundecene derivatives, structurally similar to NGP1-01, on the NMDA receptor and VGCC of synaptoneurosomes.
Access to chronic medicines: patients’ preferences for a last kilometre medicine delivery service in Cape Town, South Africa
(Springer Nature, 2021) Adams, S; Mulubwa, M; van Huyssteen, M
: Chronic patients are required to access their chronic medicines on a regular basis, often only to refill their repeat prescriptions. Adherence to chronic medicines is challenging and has stimulated health care providers to devise differentiated service delivery models of care to decentralise chronic medicine distribution to decrease the frequency of medicine collection at health care facilities. One such option includes a last kilometre medicine delivery service. This study investigated chronic patients’ preferences for a last kilometre medicine delivery service model.
Active Principles of Tetradenia riparia; II. Antispasmodic Activity of 8(14), 15-Sandaracopimaradiene-7α, 18-diol
(Georg Thieme Verlag, 1987) Van Puyvelde, Luc; Lefebvre, Romain; Mugabo, Pierre; De Kimpe, Norbert; Schamp, Niceas
Tetradenia riparia is one of the most popular medicinal plants in Rwanda. Previously, several new substances have been isolated from the leaves, including a new diterpenediol, i.e. 8(14),15-sandaracopimaradiene-7α,18-diol. This new diterpenediol exhibits a papaverine-like antispasmodic activity on the contractions of the guinea pig ileum provoked by methacholine, histamine, and barium chloride and on the noradrenaline-induced contractions of the rabbit aorta.
Acute pharmacokinetics of first line anti-tuberculosis drugs in patients with Pulmonary Tuberculosis and in patients with Pulmonary Tuberculosis co-infected with HIV
(David Publishing, 2011) Mugabo, Pierre; Hassan, Mogamat Shafick; Slaughter, R.
The aim of this study was to compare the pharmacokinetics of antituberculosis drugs in patients with pulmonary tuberculosis (PTB) and in patients with PTB and HIV during the first 24 h of treatment. Designed as a case-control study, it compares the pharmacokinetics of first line antituberculous drugs, in HIV-positive (cases) and HIV-negative (control) patients both presenting with pulmonary tuberculosis. Blood samples were collected before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 8, 12 and 24 h after administration of drugs. Drugs plasma levels were tested using HPLC assays. Results: Fourteen HIV positive (7 males and 7 females) and 17 HIV negative (9 males and 8 females) enrolled. Rifafour, a combination tablet including rifampicin, isoniazid, pyrazinamide and ethambutol was used in HIV positive patients, CD4 counts were significantly lower, renal function mildly decreased in 85% patients and moderately decreased in 7% patients. Liver function was normal in both groups. None of these patients was on other drug therapy. In the HIV positive group isoniazid T1/2 and AUC were decreased and Cl increased whereas Tmax and Cmax were unchanged. Pyrazinamide Tmax and Cmax were significantly decreased in HIV positive patients and no significant changes were noticed in the T1/2, AUC and CL. Conclusion: The study suggest that ethambutol, pyrazinamide and rifampicin pharmacokinetics was not affected by HIV infection and that isoniazid disposition is affected by HIV.
Allergic rhinitis: To sneeze or to wheeze. Pollen is the question, what is the answer?
(Medpharm Publications, 2018) Martin, Bjorn; Wehmeyer, Alexander; Upton, Edward
Allergic rhinitis, also known colloquially as hay fever, is the most common among the allergic diseases. Recent literature reports that it affects up to a tenth of the world population. Atopic diseases have a particularly high prevalence in young children which is often attributed to their immature immune systems. Traditionally, atopic diseases have plagued industrialised countries, but the burden has recently extended its reach to developing countries. Over the past few decades, there has been a marked increase in all allergy-related diseases. Supported by the advent of the Atopic March, research has been primarily directed at understanding the aetiology and pathophysiology associated with diseases stemming from atopy. In this article, we review current treatments available in South Africa and explain the pathophysiology of allergic rhinitis.
Alternative mechanisms for delivery of medication in South Africa: A scoping review
(AOSIS, 2021) Mash, Robert; Christian, Carmen; Chigwanda, Ruvimbo V
Background: The number of people in South Africa with chronic conditions is a challenge to the health system. In response to the coronavirus infection, health services in Cape Town introduced home delivery of medication by community health workers. In planning for the future, they requested a scoping review of alternative mechanisms for delivery of medication to patients in primary health care in South Africa. Methods: Databases were systematically searched using a comprehensive search strategy to identify studies from the last 10 years. A methodological guideline for conducting scoping reviews was followed. A standardised template was used to extract data and compare study characteristics and findings. Data was analysed both quantitatively and qualitatively. Results: A total of 4253 publications were identified and 26 included. Most publications were from the last 5 years (n = 21), research (n = 24), Western Cape (n = 15) and focused on adherence clubs (n = 17), alternative pick-up-points (n = 14), home delivery (n = 5) and HIV (n = 17). The majority of alternative mechanisms were supported by a centralised dispensing and packaging system. New technology such as smart lockers and automated pharmacy dispensing units have been piloted. Patients benefited from these alternatives and had improved adherence. Available evidence suggests alternative mechanisms were cheaper and more beneficial than attending the facility to collect medication. Conclusion: A mix of options tailored to the local context and patient choice that can be adequately managed by the system would be ideal. More economic evaluations are required of the alternatives, particularly before going to scale and for newer technology.
Amitriptyline prescribing in public sector healthcare facilities in the Western Cape, South Africa
(Public Library of Science, 2020) Coetzee, Renier; Johnson, Yasmina; van Niekerk, Johan
Inappropriate medication use is a major patient safety concern, especially for the elderly population. Amitriptyline is widely used in primary care in South Africa and a cross-sectional study found that amitriptyline was prescribed potentially inappropriately in 6.5% of elderly patients. An analysis of prescriptions from the Chronic Dispensing Unit in the Western Cape revealed that amitriptyline was one of the most common medicines prescribed without a suitable diagnosis listed on the prescription.
Amount of cycloserine emanating from terizidone metabolism and relationship with hepatic function in patients with drug resistant tuberculosis
(Springer, 2019) Mulubwa, Mwila; Mugabo, Pierre
The dosing of cycloserine and terizidone is the same, as both drugs are considered equivalent or used interchangeably. Nevertheless, it is not certain from the literature that these drugs are interchangeable. Therefore, the amount of cycloserine resulting from the metabolism of terizidone and the relationship with hepatic function were determined. This prospective clinical study involved 39 patients with drug-resistant tuberculosis admitted for an intensive phase of treatment. Cycloserine pharmacokinetic parameters for individual patients, like area under the curve (AUC), clearance (CLm/F), peak concentration (Cmax) and trough concentration (Cmin), were calculated from a previously validated joint population pharmacokinetic model of terizidone and cycloserine. Correlation and regression analyses were performed for pharmacokinetic parameters and unconjugated bilirubin (UB), conjugated bilirubin (CB), albumin, the ratio of aspartate transaminase to alanine aminotransferase (AST/ALT), or binding afnity of UB to albumin (Kaf), using R statistical software version 3.5.3.
Anaemia – a pale ale?
(Cogent OA, 2017) Muntingh, G. L.; Viljoen, M.
Despite some modest improvements described recently, anaemia remains a significant global public health concern affecting both developed and developing countries. It affects a quarter of the global population, including 293 million (47%) children who are younger than five years of age. A prevalence of 42% and 30% has been described in pregnant and non-pregnant women, respectively. Children and women of reproductive age are at high risk, partly because of physiological vulnerability, followed by the elderly. Africa and Asia are the most heavily affected regions, accounting for 85% of the absolute anaemia burden in highrisk groups. According to the World Health Organization global database on anaemia (1993–2005), this disorder was considered to be a moderate public health problem in South African preschool children, pregnant women and non-pregnant women of reproductive age.
An analysis of the trends, characteristics, scope, and performance of the Zimbabwean pharmacovigilance reporting scheme
(Wiley-Blackwell, 2020) Khoza, Star; Masuka, Josiah Tatenda
We aimed to determine the reporting trends and characteristics of Individual Case Safety Reports (ICSRs) from the Zimbabwean national pharmacovigilance system. ICSRs submitted to VigiBaseTM, the World Health Organisation's ICSR database between January 1993 and December 2017 were retrospectively reviewed with respect to the suspected medicine, System Organ Class (SOC), adverse drug reaction (ADR) type and seriousness, Anatomic Therapeutic Chemical (ATC) group, age, and gender. In total, 4071 ICSRs were submitted to VigiBaseTM from targeted spontaneous reporting (n = 2909; 71.5%), vaccine surveillance (n = 679; 16.7%), and passive spontaneous reporting (n = 483; 11.9%), respectively
Antibacterial Activities of Selected Green Seaweeds from West African Coast
(EC Pharmacology and Toxicology ECronicon Open Access, 2020) Agbaje-Daniels, Folashade; Adeleye, Adeyemi; Bola, Adeniyi; Francis, Seku; Beukes, Denzil; Nwankwo, Duke
The continually increasing antibiotic resistance amongst microorganisms had steered up an increased intensity in the search for new drugs. The marine environment had been reported to be a great source of novel compounds with diverse biological activities and this had engendered the attention of researcher globally, but the West African Coast despite being blessed with a variety of Macro-algae remain untapped. This study was, therefore, embarked upon to investigate the antibacterial activities of selected green algal species from the West African coast. Crude extracts of Ulva fasciata, Ulva lactuca, Chladophora vagabunda, Caulepa taxifolia, Chaetomorpha antennina and Chaetomorpha linum were obtained by maceration using Dichloromethane/methanol (DCM/MeOH), chloroform/methanol (CHL/MeOH) 90% (v/v), Ethanol and Diethyl ether as solvents. Extracts were screened against some bacterial pathogens including Gram-positive bacteria- clinical strain (Sa I), S. aureus laboratory strain (Sa II), S. aureus ATCC 25922 (Sa III), Bacillus subtilis (Bs), Streptococcus pneumonia (Sp), Streptococcus faecalis (Sf) and Mycobacterium aurum (Ma). Gram-negative test bacteria were Escherichia coli clinical (Ec I) and Escherichia coli laboratory strain (Ec II), Escherichia coli NCTC 10418 (Ec III), E. coli ATCC 25923 (Ec IV), Proteus vulgaris (Pv), Proteus mirabilis (Pm), Pseudomonas aeruginosa (Pa) Pseudomonas putida (Pp), Salmonella typhi clinical strain (St I), Salmonella typhi NCTC 8385 (St II), Serratia macerans (Sm) and Klebsiella pneumonia (Kp). Crude extracts were obtained using Antibacterial screening was carried out by disc diffusion method. The result analysis was done by mean ± SD. The result showed that all the screened algae had antibacterial activity against at least one of the test organisms. Four (57%) of the seven algal species tested demonstrated inhibitory activities against the Gram-positive test bacteria while all the seven species tested showed inhibitory activities against the Gram-negative test bacteria. Highest inhibitory zone against Gram-negative bacterial species was observed in dichloromethane/methanol extract of Caulepa taxifolia (DCCT) against E. coli measuring 14.67 mm while the highest activity against Gram-positive bacterial strain was observed in diethyl acetate extract of Chaetomorpha antennina (DECA) against S. aureus (SaII) with an inhibitory zone of 17.67 mm. Extracts of Chaetomorpha antennina showed the highest inhibitory activities in this study. The result of this study showed that extracts from species of green macro-algae from the West African Coast possess antibacterial compounds that can serve as lead drug candidates in the quest for new antibacterial therapy if well explored.
Antimycobacterial Activity, Synergism, and Mechanism of Action Evaluation of Novel Polycyclic Amines against Mycobacterium tuberculosis
(Advances in Pharmacological and Pharmaceutical Sciences, 2021-06) Kapp, Erika; Joubert, Jacques; Sampson, Samantha, L; Malan, Sarel, F; Sharma, Rajan; Warner, Digby, F; Seldon, Ronnett; Jordaan, Audrey; de Vos, Margaretha
Mycobacterium tuberculosis has developed extensive resistance to numerous antimycobacterial agents used in the treatment of tuberculosis. Insufficient intracellular accumulation of active moieties allows for selective survival of mycobacteria with drug resistance mutations and accordingly promotes the development of microbial drug resistance. Discovery of compounds with new mechanisms of action and physicochemical properties that promote intracellular accumulation, or compounds that act synergistically with other antimycobacterial drugs, has the potential to reduce and prevent further drug resistance. To this end, antimycobacterial activity, mechanism of action, and synergism in combination therapy were investigated for a series of polycyclic amine derivatives. Compound selection was based on the presence of moieties with possible antimycobacterial activity, the inclusion of bulky lipophilic carriers to promote intracellular accumulation, and previously demonstrated bioactivity that potentially support inhibition of efflux pump activity. The most potent antimycobacterial demonstrated a minimum inhibitory concentration (MIC99) of 9.6 μM against Mycobacterium tuberculosis H37Rv. Genotoxicity and inhibition of the cytochrome bc1 respiratory complex were excluded as mechanisms of action for all compounds. Inhibition of cell wall synthesis was identified as a likely mechanism of action for the two most active compounds (14 and 15). Compounds 5 and 6 demonstrated synergistic activity with the known Rv1258c efflux pump substrate, spectinomycin, pointing to possible efflux pump inhibition. For this series, the nature of the side chain, rather than the type of polycyclic carrier, seems to play a determining role in the antimycobacterial activity and cytotoxicity of the compounds. Contrariwise, the nature of the polycyclic carrier, particularly the azapentacycloundecane cage, appears to promote synergistic activity. Results point to the possibility of combining an azapentacycloundecane carrier with a side chain that promotes antimycobacterial activity to develop dual acting molecules for the treatment of Mycobacterium tuberculosis.
Antinociceptive and anti-Inflammatory activities of leaf methanol extract of cotyledon orbiculata L. (Crassulaceae)
(Hindawi, 2012) Amabeoku, George J.; Kabatende, Joseph
Leaf methanol extract of C. orbiculata L. was investigated for antinociceptive and anti-inflammatory activities using acetic acid writhing and hot-plate tests and carrageenan-induced oedema test in mice and rats, respectively. C. orbiculata (100–400 mg/kg, i.p.) significantly inhibited acetic acid-induced writhing and significantly delayed the reaction time of mice to the hot-plate-induced thermal stimulation. Paracetamol (300 mg/kg, i.p.) significantly inhibited the acetic acid-induced writhing in mice. Morphine (10mg/kg, i.p.) significantly delayed the reaction time of mice to the thermal stimulation produced with hot plate. Leaf methanol extract of C. orbiculata (50–400 mg/kg, i.p.) significantly attenuated the carrageenan-induced rat paw oedema. Indomethacin (10mg/kg, p.o.) also significantly attenuated the carrageenan-induced rat paw oedema. The LD50 value obtained for the plant species was greater than 4000 mg/kg (p.o.). The data obtained indicate that C. orbiculata has antinociceptive and anti-inflammatory activities, justifying the folklore use of the plant species by traditional medicine practitioners in the treatment of painful and inflammatory conditions. The relatively high LD50 obtained shows that C. orbiculatamay be safe in or nontoxic to mice.
Antinociceptive, anti-inflammatory and antipyretic activities of the leaf methanol extract of ruta graveolens l. (rutaceae) in mice and rats
(African Networks Ethnomedicines, 2014) Loonat, Firdows; Amabeoku, George Jimboyeka
Ruta graveolens has been used to treat toothache, earache, rheumatism and fever with little scientific evidence corroborating these uses. The leaf methanol extract of Ruta graveolens was evaluated for antinociceptive activity using the acetic acid writhing and hot-plate tests in mice, also anti-inflammatory and antipyretic activities using the carrageenan-induced oedema and E. coli-induced pyrexia tests in rats, respectively.
Application of fundamental techniques for physicochemical characterizations to understand post-formulation performance of pharmaceutical nanocrystalline materials
(MPDI, 2021) Aucamp, M; Witika, B.A; Mweetwa, L.L
Nanocrystalline materials (NCM, i.e., crystalline nanoparticles) have become an important class of materials with great potential for applications ranging from drug delivery and electronics to optics. Drug nanocrystals (NC) and nano co-crystals (NCC) are examples of NCM with fascinating physicochemical properties and have attracted significant attention in drug delivery. NCM are categorized by advantageous properties, such as high drug-loading efficiency, good long-term physical stability, steady and predictable drug release, and long systemic circulation time. These properties make them excellent formulations for the efficient delivery of a variety of active pharmaceutical ingredients (API). In this review, we summarize the recent advances in drug NCM-based therapy options. Currently, there are three main methods to synthesize drug NCM, including top-down, bottom-up, and combination methods. The fundamental characterization methods of drug NCM are elaborated. Furthermore, the applications of these characterizations and their implications on the post-formulation performance of NCM are introduced.
An assessment of social accountability among South African pharmacy schools from public domain information
(AFAHPER-SD, 2017) Bheekie, Angeni; Van Huyssteen, Mea
Global health education reform requires training institutions to align their education, service and research activities with the values of social accountability, which include relevance, equity, quality and effectiveness. The alignment with these values aims to ensure graduates who are competent to meet society’s priority health needs, especially those of marginalised and underserved communities. This study aimed to qualitatively assess the alignment of activities of the nine South African pharmacy schools with the values of social accountability from information and evidence available in the public domain. Data were collected from pharmacy schools’ websites, and related publications and newsletters. Information was grouped into predetermined categories representing the different values of social accountability. A scoring rubric was adapted that assessed the alignment of the information and evidence collected to the values of relevance equity and quality. Each pharmacy school’s information was initially reviewed and scored by three independent reviewers. Each of the reviewers cross-checked each other’s allocated scores and any variations in scores were settled via consensus between the reviewers. The information of six pharmacy schools was assessed. For relevance, pharmacy schools scored over 50% and above for all their activities. For equity, schools showed most variation in their educational activities, and least variation in their service activities. For quality, schools showed most consistency with education and service activities but most variation occurred in the quality of services. Information from the public domain may be useful in assessing social accountability. The depth of information that schools could share publicly remains a key question.
Assessment of thermal and hydrolytic stabilities and aqueous solubility of artesunate for formulation studies
(AAPS PharmSciTech, 2023) Aucamp, M; Bezuidenhout, J. W.; Stieger, N; Liebenberg, W; Haynes, R. K
For the purpose of establishing the optimum processing parameters and storage conditions associated with nanolipid formulations of the artemisinin derivative artesunate, it was necessary to evaluate the thermal stability and solubility profiles of artesunate in aqueous solutions at various temperatures and pH. The effect of increased temperature and humidity on artesunate was determined by storing samples of the raw material in a climate chamber for 3 months and analyzing these by an established HPLC method
Assessment of Vancomycin Pharmacokinetics and Dose Regimen Optimisation in Preterm Neonates
(Springer Nature, 2020) Mulubwa, Mwila; Griesel, Heletje Aletta; Mugabo, Pierre E.
The pharmacokinetics of vancomycin, a drug used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), varies between paediatric and adult patients. The objective of this study was to assess the pharmacokinetics of vancomycin in preterm neonates and determine the optimum dose regimen.

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