Higijenski uvjeti u osnovnim i srednjim školama na području Splitsko-dalmatinske županije

This paper gives an assessment of hygienic conditions found in 22 primary and 12 secondary schools in the city of Split during the school year 1990/91. The data were compared with the results of a similar investigation carried out in eight primary schools in the neighbouring Sinj area. The assessment consisted of the examination of the facilities, questionnaires, and microbiological analysis of numerous samples. Most schools failed to meet the recommendations for hygienic and sanitary maintenance, particularly with regard to sanitary facilities for students and staff. Exposure to noise, inadequate lighting, and poor maintenance of gymnasiums were noticed. Of the total number of smears taken from the students’ hands and various surfaces in schools in the Sinj area, group D streptococcus was isolated in 62% and E. coli in 43% of samples. Both bacteria indicate faecal contamination. The data suggest a low level of personal and general hygiene in schools. It is necessary to improve the hygienic conditions in the schools of the Split and Sinj area and to focus on health education. It would reduce the risk of intestinal and respiratory infectious diseases and potential sight and hearing impairments in students.Tijekom 1990./91. školske godine istraživani su ekološko-higijenski uvjeti u 22 osnovne škole i 12 srednjoškolskih centara u gradu Splitu. Podaci su uspoređeni sa sličnim istraživanjem provedenim 1995./96. školske godine u osam osnovnih škola na sinjskom području. Cilj rada bio je evaluirati učinke preventivnih mjera u sprječavanju bolesti i stanja koja mogu nastati zbog loših higijenskih uvjeta u školskoj sredini. Ekološko-higijenski uvjeti ocijenjeni su na temelju pregleda objekata, anketnog upitnika i mikrobiološkog ispitivanja. Većina škola nije zadovoljavala preporuke higijensko-sanitarnog održavanja školskog prostora, osobito sanitarnih čvorova za učenike i nastavnike. Uočeni su i nedostaci kao izloženost buci, neadekvatna rasvjeta te nedovoljan broj, loša kvaliteta i održavanje dvorana za tjelesni odgoj. Od ukupnog broja uzetih brisova u školama na sinjskom području iz 62% izoliran je streptokok grupe D, a iz 43% E. coli. Navedene bakterije su pokazatelji fekalnog onečišćenja. Dobiveni podaci upućuju na nisku razinu osobne i opće higijene u školama. Potrebno je sanirati građevinsko-tehničko i ekološko-higijensko stanje u školama na splitskom i sinjskom području te provoditi zdravstveni odgoj. To bi smanjilo rizik pojave crijevnih i respiratornih zaraznih bolesti te mogućih oštećenja vida i sluha učenikâ

Design, synthesis and biological evaluation of novel primaquine-cinnamic acid conjugates of the amide and acylsemicarbazide type

In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a–k) or via a spacer (compounds 7a– k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ- CAD amides 3a–k were prepared by a simple one- step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7a–k included activation of PQ with benzotriazole, preparation of PQ- semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c–e), benzodioxole (7f), p- Cl (7g) and m-CF3 (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%–89%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC50 = 10 μΜ). The performed biological tests gave evidence of acylsemicarbazide functional group as superior binding group in PQ-CAD conjugates

Machine learning prioritizes synthesis of primaquine ureidoamides with high antimalarial activity and attenuated cytotoxicity

Primaquine (PQ) is a commonly used drug that can prevent the transmission of Plasmodium falciparum malaria, however toxicity limits its use. We prepared five groups of PQ derivatives: amides 1a-k, ureas 2a-k, semicarbazides 3a,b, acylsemicarbazides 4a-k and bis-ureas 5a-v, and evaluated them for antimalarial activity in vitro against the erythrocytic stage of P. falciparum NF54. Particular substituents, such as trityl (in 2j and 5r) and methoxybenzhydryl (in 3b and 5v) were associated with a favorable cytotoxicity-to-activity ratio. To systematically link structural features of PQ derivatives to antiplasmodial activity, we performed a quantitative structure-activity relationship (QSAR) study using the Support Vector Machines machine learning method. This yielded a highly accurate statistical model (R2 = 0.776 in cross-validation), which was used to prioritize novel candidate compounds. Seven novel PQ-ureidoamides 10a-g were synthesized and evaluated for activity, highlighting the benzhydryl ureidoamides 10e and 10f derived from p-chlorophenylglycine. Further experiments on human cell lines revealed that 10e and 10f are an order of magnitude less toxic than PQ in vitro while having antimalarial activity indistinguishable from PQ. The toxicity profile of novel compounds 10 toward human cells was particularly favorable when the glucose-6-phosphate dehydrogenase (G6PD) was inhibited, while toxicity of PQ was exacerbated by G6PD inhibition. Our work therefore highlights promising lead compounds for the development of effective antimalarial drugs that may also be safer for G6PD-deficient patients. In addition, we provide computational inferences of antimalarial activity and cytotoxicity for thousands of PQ-like molecular structures

Design, synthesis and biological evaluation of novel primaquine-cinnamic acid conjugates of the amide and acylsemicarbazide type

In this paper design and synthesis of a scaffold comprising primaquine (PQ) motif and cinnamic acid derivatives (CADs) bound directly (compounds 3a-k) or via a spacer (compounds 7a-k) are reported. In the first series of compounds, PQ and various CADs were connected by amide bonds and in the second series by acylsemicarbazide functional groups built from the PQ amino group, CONHNH spacer and the carbonyl group originating from the CADs. PQ-CAD amides 3a-k were prepared by a simple one-step condensation reaction of PQ with a series of CAD chlorides (method A) or benzotriazolides 2 (method B). The synthesis of acylsemicarbazides 7a-k included activation of PQ with benzotriazole, preparation of PQ-semicarbazide 6 and its condensation with CAD chlorides 4. All synthesized PQ-CAD conjugates were evaluated for their anticancer, antiviral and antioxidative activities. Almost all compounds from series 3 were selective towards the MCF-7 cell line and active at micromolar concentrations. The o-fluoro derivative 3h showed high activity against HeLa, MCF-7 and in particular against the SW 620 cell line, while acylsemicarbazide 7f with a benzodioxole ring and 7c, 7g and especially 7j with methoxy-, chloro- or trifluoromethyl-substituents in the para position showed high selectivity and high inhibitory activity against MCF-7 cell line at micromolar (7c, 7f, 7g) and nanomolar (7j) levels. Acylsemicarbazide derivatives with trifluoromethyl group(s) 7i, 7j and 7k showed specific activity against human coronavirus (229E) at concentrations which did not alter the normal cell morphology. The same compounds exerted the most potent reducing activity in the DPPH test, together with 7d and 7g, while methoxy (compounds 7c-e), benzodioxole (7f), p-Cl (7g) and m-CF₃ (7i) acylsemicarbazides and amide 3f presented the highest LP inhibition (83%-89%). The dimethoxy derivative 7d was the most potent LOX inhibitor (IC50 = 10 μΜ). The performed biological tests gave evidence of acylsemicarbazide functional group as superior binding group in PQ-CAD conjugates.status: publishe