In silico pharmacokinetic and molecular docking studies of N-cinnamoyltetraketide derivatives as inhibitors of cyclooxygenase-2 enzyme

Recent phytochemical analysis of Toussaintia orientalis leaves yielded series of novel bioactive N-cinnamoyltetraketide derivatives namely toussaintines A-G (t_1 - t_8) some portraying cytotoxicity against the triple negative aggressive human breast cancer cell line (MDA-MB-231) among other potencies. Despite having broad bioactivity spectrum, their general drug-likeness profiles and mode of action (simulated or actual) targeting any enzyme remains uninvestigated. In silico pharmacokinetic, drug-likeness descriptors and molecular docking of the compounds t_1-t_8 targeting inhibition of cyclooxygenase-2 (COX-2) enzyme were evaluated. The Lipinski Rule of Five heralded the pharmacokinetic properties of the studied metabolites. The studied compounds were docked with COX-2 following already established protocol. ADMET descriptors fell within the recommended range, except for compound t_3 that was predicted to potentially have positive blood brain barrier (BBB+) penetration. Docking studies indicated N-cinnamoyltetraketide derivatives as potential inhibitors of COX-2 enzyme.  Compounds t_3 and t_5 showed lower binding energy of -13 and -12.3 kcal/mol, respectively, being closely comparable to celecoxib (-12.3 kcal/mol) indicating compatibility with the protein receptor. The findings provide baseline information on drug or lead-likeness and potential mode of action of the studied molecules towards inhibition of COX-2 enzyme.Keywords: N-cinnamoyltetraketide derivatives; molecular docking, ADMET, in silico, COX-2

Chemical Constituents and Antimicrobial Evaluation of Selected Aloe vera Branded Commercial Products in Tanzania

Chemical compositions and antimicrobial activities of twenty-two Aloe vera branded commercial products in Tanzania, a case of marketed soaps, creams, lotions, petroleum jelly, toothpastes and hair conditioner products in Dar es Salaam, were investigated. Chemical compositions were analysed using gas chromatography-mass spectrometry (GC-MS) whereas antimicrobial activities were evaluated using agar dilution method against four bacteria species, namely Staphylococcus aureus, Escherichia coli, Klebsiella pneumoneae and Salmonella typhi) and two fungal species Candida albicans and Cryptococcus neoformans. The GC-MS analysis revealed the presence of seven non-polar constituents, namely methyl palmitate, 9-octadecenoic acid methyl ester, methyl stearate, tetratetracontane, hexacosane, and pentacosane and methyl tetradecanoate as the most common ingredients among the products. Eleven compounds were detected in both the commercial products and reference A. vera extracts. The commercial products AVC5 and AVL3 inhibited the growth of E. coli and S. typhi at minimum inhibitory concentrations (MICs) of 7.5 and 12.5% (v/v), respectively, whereas AVC2 and AVC5 inhibited the growth of C. albicans and C. neoformans at 5.0% (v/v). AVC6 had 7.5 and 15.0% (v/v) MICs for C. neoformans and C. albicans, respectively. Other commercial products and the reference A. vera extracts were inactive against the tested microbes at a screening concentration of 10.0 mg/mL.  Keywords: Aloe vera; Aloe vera branded commercial products; GC-MS; Antimicrobia

Tanning capacity of Tessmannia burttii extracts: the potential eco-friendly tanning agents for the leather industry

The research article was published in the journals of Leather Science and Engineering 2021In the present study, the tannins from stem and root barks of Tessmannia burttii Harms (Caesalpiniaceae), a plant species abundantly growing in Tanzania and other parts of Africa, were investigated for their suitability in hides tanning. Tannin powder was extracted at selected temperatures (30, 50 and 80 °C) and the influence of each temperature on the crosslinking capacity was evaluated. The interaction mechanism between hide powder collagen and the tannins was studied by Differential Scanning Calorimetry (DSC), trinitrobenzensulfonic (TNBS) acid assay and amino acid hydrolysis methods. Extraction temperatures showed low influence on crosslinking capacity of the tannins. However, extract obtained at 50 °C exhibited best performance in terms of gap size between T onset and T peak. The stem bark extract yield was higher than that from the root bark, but both were within the recommended ranges. The tannin content (61%) of T. burttii stem bark extract was above recommended value (10%), whereas its total phenolic content and total flavonoic content were found to be above that of commercial Acacia mearnsii tannin. The study of cross-linking parameters as a function of pH showed cross-linking to occur via a covalent mechanism at the basic amino groups. However, the bonds were not resistant to acid hydrolysis. The observed interaction mechanism indicated that tannins from stem and root barks of T. burttii belong to the condensed tannin, similar to A. mearnsii (black wattle), a commercial tannin source that was used in this study as a reference. Findings from this study depict that T. burttii extracts are auspicious eco-friendly alternative source of vegetable tannins to overcome the use of chromium salts in the leather industry

In vivo antimycobacterial studies of toussaintine A-chitosan nanocomposites

Chitosan (CS, molecular weight (MW) 20.2 kDA, stability of 210 °C and degree of deacetylation (DD) 73.31%) was obtained by deacetylation of chitin extracted from shrimp (Litopenaeus vannamei) shell wastes. The encapsulation of the studied bioactive natural product, toussaintine A (TA) isolated from the leaves of Toussaintia orientalis, on a chitosan-tripolyphosphate (CS/TPP) nanoformulation was attained through ionotropic gelation. Characterization of pure CS, CS/TPP and TA-CS/TPP nanocomposites was carried out by FTIR and SEM. The encapsulation efficiency and loading capacity of the TA were 69.33 and 0.46%, respectively. The in vitro release kinetics established an initial release of 27% of TA in the initial six hours followed by a slow and maintained release up to 72 h. The in vivo antimycobacterial acitivities of both TA and TA-CS/TPP nanocomposites against Mycobacterium indicus pranii (MIP) employing Galleria mellonella larvae as an infection model were evaluated. TA-CS/TPP nanocomposite formulations exhibited remarkable effectiveness against MIP than free TA.Keywords: Toussaintine A; chitosan; nanocomposites, antimycobacterial; Galleria mellonell

Bioactivities of extracts, debromolaurinterol and fucosterol from macroalgae species

Parasitic diseases including malaria, and other numerous microbial infections and physiological diseases are threatening the global population. Tanzanian coast shores are endowed with a variety of macroalgae (seaweeds), hitherto unsystematically explored to establish their biomedical potentials. Thus, antiplasmodial activity using malarial imaging assay, antimicrobial activity using microplate dilution technique, antioxidant activity using DPPH radical scavenging method and cytotoxicity using brine shrimp test were carried out on crude extracts from the selected species of algae (Acanthophora spicifera, Cystoseira myrica, Cystoseira trinodis, Laurencia filiformis, Padina boryana, Sargassum oligocystum, Turbinaria crateriformis, Ulva fasciata and Ulva reticulata) occurring along the coast of Tanzania. The extracts showed antimicrobial activities with MIC ranging from 0.3- 5.0 µg/mL against Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Escherichia coli, Candida albicans and Cryptococcus neoformans; DPPH radical scavenging activity at EC50 1.0- 100 µg/mL and cytotoxicity on brine shrimp larvae with LC50 value ranging from20 - 1000 µg/mL. The extracts from C. myrica and P. boryana inhibited growth of Plasmodium falciparum (3D7 strain) by 80 and 71%, respectively at 40 µg/mL while a sesquiterpene debromolaurinterol (1) which was chromatographically isolated from C. myrica exhibited antiplasmodial activity with IC50 20 µM whereas a sterol fucosterol (2) from P. boryana showed weak activity at 40 µM. Bioactivities portrayed by the investigated extracts indicate their ingredients as potential sources of bioactive agents that warrant further explorations.Keywords:     Macrolgae, antiplasmodial, antimicrobial, antioxidant, cytotoxicity, DPPH radical scavenging, debromolaurinterol and fucosterol

Solvent effects on host-guest residence time and kinetics: further insights from metadynamics simulation of Toussaintine-A unbiding from chitosan nanoparticle

This research article published by Springer Nature Switzerland AG., 2021Solvents play an important role in host-guest intermolecular interactions. The kinetics and residence time of Toussaintine-A (TouA) unbinding from chitosan was investigated by means of well-tempered metadynamics and thermodynamic integration using two solvents, polar aprotic (DMSO), and polar protic (water). The kinetic rates were found to be strongly dependent on the solvent polarity; hence, the unbinding rate proceeded much faster in DMSO compared to water. DMSO tends to participate less in a chemical reaction by weakening the intermolecular interaction between chitosan and TouA due to lack of acidic hydrogen resulting in a reduction of the transition state. On the other hand, water, which ought to donate hydrogen atoms, sustains a strong interaction and hence large barrier heights. Consequently, this reduces the unbinding rate and increases the residence time. Binding free energy from thermodynamic integration suggests a thermodynamic stable chitosan-TouA complex in water than in DMSO

Alternative tanning technologies and their suitability in curbing environmental pollution from the leather industry: A comprehensive review.

This research article published by Elsevier Ltd., 2020Chrome tanning remains the most favourite technology in the leather industry worldwide due to its ability to produce leather with attributes desirable for high-quality leather such as excellent hydrothermal stability, better dyeing characteristics and softness. Nevertheless, the technology has been censured globally for its severe environmental detriments and adverse effects on human health and other organisms. Developing alternative eco-friendly tanning technologies capable of producing leather of high quality has remained a challenging scientific inquiry. This review article provides an assessment of various eco-friendly tanning attempts geared towards improving or replacing the chrome technology without compromising the quality of the produced leather. The reviewed publications have ascertained that, these attempts have been centred on recycling of spent liquors; chromium exhaustion enhancement and total replacement of chromium salts. The research gaps and levels of key environmental pollutants from the reviewed technologies are presented, and the qualities of the leather produced from these technologies are highlighted. Of all the examined alternative technologies, total replacement of chromium salts sounds ideal to elude adverse effects associated with chrome tanning. Combination tanning, which implies blending two tanning agents that individually cannot impart desired properties to the leather, is anticipated to be an alternative technology to chrome tanning. Apart from being an eco-friendly technology, combination tanning produces leather with similar features to those produced by chrome tanning. In this regard, blending vegetable tannins with aluminium sulphate provides a promising chrome-free tanning technology. However, further studies to optimize combination tanning technologies to suit industrial applications are highly recommended

Synthesis of amine functionalized mesoporous silicas templated by castor oil for transesterification

Mesoporous silicas were synthesized via a surfactant-templated sol-gel route using castor oil as the templating agent under acidic medium. The resulting silicas were subsequently amine functionalized with 3-aminopropyltriethoxysilane (NH2-MTS), [3-(2-aminoethylamino)-propyl]trimethoxysilane (NN-MTS), and [3-(diethylamino)propyl]trimethoxysilane(DN-MTS) to introduce surface basicity. Surface physicochemical properties were characterized by field emission gun scanning electron microscopy (FEGSEM), nitrogen porosimetry, X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), X-ray diffraction (XRD), and diffuse reflectance infrared fourier transform spectroscopy (DRIFTS). As-synthesised materials exhibit type IV adsorption-desorption isotherms characteristic of mesoporous structures. Clusters of spherical shaped materials were observed by FEGSEM, suggesting growth of silica occurs within colloidal dispersions. High-resolution N 1s XP spectra and DRIFT spectra confirmed the presence of amine groups in the organo-amine functionalised mesoporous silicas. The amine functionalised mesoporous silicas were active for the transesterification of tributyrin with methanol, with conversion found to increase from NH2-MTS< NN-MTS< DN-MTS

Assessment of quality of obstetric care in Zimbabwe using the standard primipara

Background To improve maternity services in any country, there is need to monitor the quality of obstetric care. There is usually disparity of obstetric care and outcomes in most countries among women giving birth in different obstetric units. However, comparing the quality of obstetric care is difficult because of heterogeneous population characteristics and the difference in prevalence of complications. The concept of the standard primipara was introduced as a tool to control for these various confounding factors. This concept was used to compare the quality of obstetric care among districts in different geographical locations in Zimbabwe. Methods This was a substudy of the Zimbabwe Maternal and Perinatal Mortality Study. In the main study, cluster sampling was done with the provinces as clusters and 11 districts were randomly selected with one from each of the nine provinces and two from the largest province. This database was used to identify the standard primipara defined as; a woman in her first pregnancy without any known complications who has spontaneous onset of labour at term. Obstetric process and outcome indicators of the standard primipara were then used to compare the quality of care between rural and urban, across rural and across urban districts of Zimbabwe. Results A total of 45,240 births were recruited in the main study and 10,947 women met the definition of standard primipara. The maternal mortality ratio (MMR) and the perinatal mortality rate (PNMR) for the standard primiparae were 92/100000 live births and 15.4/1000 total births respectively. Compared to urban districts, the PNMR was higher in the rural districts (11/1000 total births vs 19/ 1000 total births, p < 0.001). In the urban to urban and rural to rural districts comparison, there were significant differences in most of the process indicators, but not in the PNMR. Conclusions The study has shown that the standard primipara can be used as a tool to measure and compare the quality of obstetric care in districts in different geographical areas. There is need to explore further how the quality of obstetric care can be improved in rural districts of Zimbabwe

Suitability of selected vegetable tannins traditionally used in leather making in Tanzania

This research article published by Elsevier Ltd., 2020The use of chromium salt has dominated in tanning industry worldwide due to its high versatility in quality leather production. However, Environmental concerns of chromium have shifted the interest of current research to chrome-free and greener chemical processing options. Vegetable tannins, especially when used in combination with some benign metals, have been proven to be environmentally safe and manageable, while producing good quality leather with similar shrinkage temperature as that of chromium tanned. As such, shortage of vegetable tannin supply necessitates characterization of non-commercialized sources locally available to feed cottage tanneries. In the present work, extracts from Acacia mearnsii, Acacia xanthophloea, Euclea divinorum and Euclea racemosa, leached by simple technique at 30–80 °C temperature range were characterized for extract yield, tannin, total flavonoid and phenolic contents, crosslinking ability as well as properties of tanned leather. Results indicate that at 50 °C extraction temperature, A. xanthophloea bark gave extract with properties similar to that of A. mearnsii (commercialized source of tannin). Extract from E. divinorum bark contain fairly less extract yield, tannin, total flavonoid and phenolic contents than that of A. mearnsii, but had good crosslinking ability and tanning performance similar to that of A. mearnsii when used in combination with Aluminium Sulphate [Al2(SO4)3]. The 2% Aluminium Oxide (Al2O3) equivalent was established to be optimal dose of Al2(SO4)3 for extract pre-treatment. E. racemosa barks have high extract yield, but very low crosslinking ability, making it not suitable as a tannin source. This work provides useful information on the potential source of tannins for cottage leather industries in Tanzanian and beyond