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

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

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

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

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

Valorization of rice husk silica waste:Organo-amine functionalized castor oil templated mesoporous silicas for biofuels synthesis

Rice husk is a rich source of waste silica which has potential for application in the preparation of porous materials for use as catalyst supports or sorbents. Here we report on the synthesis of rice husk silica (RHS) and mesoporous templated rice husk silica (MT-RHS) using sodium silicate, obtained from rice husk ash, and castor oil as a pore directing agent. The resulting silicas were functionalized with 3-aminopropyltriethoxysilane (APTS) or 3-diethylaminopropyltrimethoxysilane (DEPA), and their catalytic activity evaluated in the transesterification of model C4–C12 triglycerides (TAG) to their corresponding fatty acid methyl esters, of relevance to biodiesel synthesis. Castor oil templating enhances the surface area of rice husk silica, and introduces uniform 4 nm mesopores, albeit as a disordered pore network. Post-synthetic grafting of silica by APTS or DEPA resulted in base site loadings of 0.5 and 0.8 mmolg−1 respectively on RHS and MT-RHS. Turnover frequencies of amine-functionalized MT-RHS were 45–65% greater than those of their amine-functionalized RHS counterparts for tributyrin transesterification. Switching from a primary (APTS) to tertiary (DEPA) amine increased activity three-fold, delivering 80% tributyrin conversion to methyl butyrate in 6 h. DEPA-MT-RHS was effective for the transesterification of C8 and C12 triglycerides, with methyl caproate and methyl laurate selectivities of 93% and 71% respectively in 24 h

Genus <i>Monanthotaxis</i>: a review on distribution, ethnomedicinal uses and phytochemistry

This article reviews the geographical distribution, ethnomedicinal applications, and phytochemistry of the genus Monanthotaxis Baill, tribe Uvariae of the family Annonaceae. The reviewed works of literature were collected from various electronic databases including Google Scholar, PubMed, Science Direct, The International Plant Names Index (IPNI), and Research Gate. During this review, ninety-eight species of the genus Monanthotaxis were found to be widely distributed in tropical Africa. Some of those species are used in folkloric medicine by various communities to manage diseases and disease conditions such as fever, vomiting, headache, stomach-ache, malaria, helminthiasis, and hysteria. In the past 44 years (1979 to 2023), one hundred and nineteen secondary metabolites with different biomedical potentials have been reported from this genus. The reported compounds are categorised into flavonoids, alkaloids, terpenoids, polyoxygenated cyclohexane, and cyclohexene derivatives, benzyl derivatives, cinnamic acid derivatives, and stilbenoids. Most of the reported compounds showed an array of bioactivities corroborating the use of some members of the genus in folkloric medicine.</p

Polyamidoamine Dendrimers for Enhanced Solubility of Small Molecules and Other Desirable Properties for Site Specific Delivery: Insights from Experimental and Computational Studies

Clinical applications of many small molecules are limited due to poor solubility and lack of controlled release besides lack of other desirable properties. Experimental and computational studies have reported on the therapeutic potential of polyamidoamine (PAMAM) dendrimers as solubility enhancers in pre-clinical and clinical settings. Besides formulation strategies, factors such as pH, PAMAM dendrimer generation, PAMAM dendrimer concentration, nature of the PAMAM core, special ligand and surface modifications of PAMAM dendrimer have an influence on drug solubility and other recommendable pharmacological properties. This review, therefore, compiles the recently reported applications of PAMAM dendrimers in pre-clinical and clinical uses as enhancers of solubility and other desirable properties such as sustained and controlled release, bioavailability, bio-distribution, toxicity reduction or enhancement, and targeted delivery of small molecules with emphasis on cancer treatment

Draft genome sequence of limnospira sp. strain BM01, isolated from a hypersaline lake of the momela ecosystem in tanzaniaac

The genus Limnospira includes cyanobacterial species used for industrial production of dietary supplements and nutraceutical agents. The metagenomeassembled genome of Limnospira sp. strain BM01 from Big Momela Lake, Tanzania, was 6,228,312 bp long with a GC content of 44.8% and carried 4,921 proteins and 52 RNA genes, including 6 rRNA genes