Editorial: Promoting laboratory-based scientific research in Kenya

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Syntheses and characterization of water-soluble phythalocyanines for diagnosis and treatment of cancer

Ongarora, Benson Getenga, B.S., Moi University, 2005 Doctor of Philosophy, Fall Commencement, 2012 Major: Chemistry Syntheses and Characterization of Water-Soluble Phthalocyanines for Diagnosis and Treatment of Cancer Dissertation directed by Professor M.Graҫa H. Vicente Pages in dissertation, xi. Words in abstract, 251. ABSTRACT Chapter 1 describes the general properties of phthalocyanines, synthesis of metallo-phthalocyanines, their photophysical features and their uses. The concepts of PDT and targeted therapeutics are also introduced. Chapter 2 describes the syntheses, characterization, photophysical studies and biological evaluation of cationic phthalocyanines. The trimethylaminophenoxy substituted phthalocyanines were synthesized through statistical condensation method, which gave a statistical mixture of isomers. Di-cationic phthalocyanines were found to be more cytotoxic. The amphiphilicity of the phthalocyanines played an important role. Chapter 3 covers the conjugation of phthalocyanines to peptides and is in pursuit of targeted therapeutics. The conjugation of two peptides, EGFR L1 (six amino acid residues) and EGFR L2 (twelve amino acid residues), gave conjugates with different charge, length, and hydrophobicity. The bioconjugates were synthesized via SPS method using typical peptide coupling agents. Cellular and animal studies are described for the conjugates. Chapter 4 is a description of the syntheses and characterization of pure regiomeric phthalocyanines. Previous chapters described, mostly, statistical mixture of Pcs. In this chapter, strategy to the synthesis of monomeric isomers and their characterization is presented. Chapter 5 describes the syntheses, characterization and cellular studies of a series of di-cationic and pegylated phthalocyanines. Statistical condensation was used in the synthesis of macrocycles. Phthalocyanines with cationic charge at close proximity and on α-substitution position of the macrocycle were found to be more cytotoxic. In addition, Pc-antibody bioconjugates are discussed. The biological studies are described for both cationic Pcs and Pc-conjugates. Just like Chapter 3, this chapter is also in pursuit of targeted therapeutics

Quality of dairy milk obtained from automated dispensing machines in Nairobi County, Kenya

Dairy milk is one of the most widely consumed food products. Owing to its rich nutritional value, milk acts as a good medium for microbial growth. Suppliers have been known to adulterate milk with various chemicals for preservation, increasing viscosity and whitening, among other reasons. Increasingly, residents of big cities such as Nairobi County are purchasing their milk from automated milk dispensing machines, which obtain milk from small scale dairy farmers. This study set out to determine the quality of milk purchased from automated milk dispensing machines in selected settlements in Nairobi County. Microbial quality was determined using the methylene blue reduction test while established chemical methods were employed in the tests for hydrogen peroxide and formaldehyde. Twenty one samples, representing 70% of the samples analyzed, tested positive for hydrogen peroxide while only 5 (16.7%) and 7 (23.3%) samples tested positive for formaldehyde and microbial contamination, respectively. These results indicate that there is need to improve the quality of milk dispensed in automated dispensing machines.Keywords: Milk, adulteration, formaldehyde, hydrogen peroxid

Formulation and in vitro evaluation of a mucoadhesive metronidazole dental gel for oral application

Periodontitis is inflammation of the supporting tissues of the teeth caused by microorganisms found in plaque. Metronidazole is commonly used for the treatment of periodontal diseases like gingivitis and periodontitis. Treatment of periodontaldisease orally using metronidazole tablets for a prolonged period can cause gastrointestinal disturbances in patients leading to poor patient compliance. This project aimed at formulating a mucoadhesive metronidazole dental gel preparation safe for use on the gums as a form of prophylaxis against infections caused by anaerobic bacteria after dental procedures. Formulation of the gel was carried out in the laboratory using different concentrations of Carbopol® 971P NF. The gels obtained showed acceptable uniformity of content, pH, spreadability, in vitro diffusion characteristics as well as mucoadhesive and organoleptic properties.Keywords: Metronidazole, mucoadhesive gel, oral applicatio

Antimicrobial activity of extracts and phytosterols from the root bark of Lonchocarpus eriocalyx

The root bark of Lonchocarpus eriocalyx was dried, powdered and extracted using chloroform, methanol and hot water. The extracts exhibited antibacterial activity against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus and antifungal activity against Saccharomyces cerevisiae. The decoction (100mg/ml) was more active than the chloroform and methanol extracts against the four microorganisms. Chromatographic fractionation of the chloroform extract using normal phase silica yielded the phytosterols lupeol and lupenone. At 100 mg/ml, the compounds were active against all the four microorganisms, with lupeol being more active than lupenone. This is the first report of the isolation of lupenone from Lonchocarpus eriocalyx.Keywords:  Lonchocarpus eriocalyx, lupeol, lupenone, antimicrobial activit

A stability indicating liquid chromatography method for the assay of rufinamide bulk material and tablets

A simple, rapid, isocratic stability indicating reverse phase liquid chromatography method was developed for the assay of rufinamide bulk drug and tablets. The method achieved adequate resolution of rufinamide, related substances A and B as well as laboratory generated degradation products. The method uses a Phenomenex® Hyperclone BDS C-18 column (250 × 4.6 mm, 5 μ) maintained at 35 °C and a mobile phase composed of methanol-0.1 M octane sulfonic acid-0.1 M KH2PO4, pH 6.5-water (30:10:5:55, % v/v/v/v) delivered at a flow rate of 1.0 ml/min. The eluents were monitored by means of ultraviolet detection at 210 nm. During validation, the method satisfied the International Conference on Harmonization acceptance criteria for linearity sensitivity, precision, accuracy, and robustness. The developed method may be applied in the routine analysis of rufinamide bulk material and tablets as well as stability studies.Keywords: Rufinamide, stability indicating method, related compoun

Jatropha curcas poisoning in children in western Kenya – a case report

A case of Jatropha poisoning in children in Kakamega Division, Kenya is reported. A literature review showed that this plant has caused poisoning in children in other countries. The circumstances leading to poisoning, time to onset of symptoms and the clinical manifestation of poisoning in all cases reported in literature as well as in the present case report show a striking similarity. In all cases, gastrointestinal disturbance (vomiting, abdominal pain, nausea and diarrhoea) were prominent and these were attributed to curcin a toxalbumin present in the seeds of Jatropha curcas. Dehydration and electrolyte imbalance is a consequence of vomiting and diarrhoea. Supportive treatment leads to full recovery, usually within 24 hours.Keywords:  Jatropha curcas, poisoning, plant poisoning, curci

Antimalarial drug rescue through safety improvement: design, synthesis and evaluation of amaodiaquine analogues

Includes bibliographical references.Malaria is a major cause of morbidity and mortality globally, resulting in over 200 million cases and 650, 000 deaths in 2010 according to the 2012 WHO Malaria Report. Furthermore, malaria endemicity is associated with poor economic growth. One of the greatest challenges facing malaria chemotherapy is the emergence of Plasmodium strains resistant to all known clinically used antimalarials. This underscores the need for the development of new drugs that retain efficacy against the resistant parasites. In this study, analogue-based drug design was employed as a form of drug ‘rescue’ in the development of novel potential antimalarials. The main aim was to design and synthesize analogues of the 4-aminoquinoline drug amodiaquine with potentially improved safety and efficacy profiles using prior knowledge of the drug metabolism and pharmacokinetics (DMPK), toxicity and efficacy profile of the drug. A representative set of compounds in four different series was synthesized in which the 4-aminoquinoline ring was coupled with benzothiazole, benzimidazole, benzoxazole and pyridyl rings bearing different aliphatic amines and diamines. The chemistry involved aromatic nucleophilic substitution reactions and hydrogenation of nitro aromatic compounds. Benzothiazole and benzoxazole analogues with a tertiary protonatable nitrogen were found to possess potent antiplasmodial activity against the drug resistant W2 and K1 Plasmodium falciparum strains

Isolation, characterization and antiplasmodial activity of phytochemical constituents from Monanthotaxis parvifolia (Oliv.) Verdc ssp. kenyensis Verdc

Fractionation of the methanol extract of the leaves of Monanthotaxis parvifolia (Oliv.) Verdc ssp. kenyensis Verdc (Annonaceae) by preparative high performance liquid chromatography yielded seven fractions from which two phytochemical constituents were isolated and identified as quercetin-3-O-β-galactopyranoside (hyperoside) and quercetin-3-O-α-arabinofuranoside (avicularin) on the basis of spectroscopic data analysis and comparison with published data for the known compounds. This is the first report of the isolation of these compounds from Monanthotaxis parvifolia. Hyperoside and avicularin exhibited moderate antiplasmodial activity against chloroquine sensitive (D10) and chloroquine resistant (Dd2) Plasmodium falciparum strains (IC50 = 10.85 - 38.07 μg/ml). Hyperoside had selectivity index greater than 10 when assayed for cytotoxicity on Chinese hamster ovarian cell line.Keywords:  Monanthotaxis parvifolia (Oliv.) Verdc ssp. kenyensis Verdc, quercetin glycosides, antiplasmodial activity, cytotoxicit

Synthesis and investigation of phthalocyanine-biotin conjugates

An isothiocyanato-functionalized phthalocyanine (Pc) was synthesized in good yield from the corresponding amine-substituted Pc. This Pc reacted with ethanolamine, biotin hydrazine, and biotin diethylamine under mild conditions (room temperature in DMF or DMSO in the presence of TEA) to produce the corresponding thiourea products in 60-75% yields. All Pcs showed intense Q absorptions in DMF around 677 nm, emissions centered at 683 nm, and fluorescence quantum yields in the range 0.18-0.27. The Pcs were phototoxic to human carcinoma HEp2 cells (IC50 similar to 7 at 1.5 J/cm(2)) and localized in multiple organelles, including the lysosomes, Golgi and ER. One biotin-Pc conjugate was injected via tail vein into nude mice bearing HT-29 tumors and demonstrated selective localization in the tumor tissue