Novel sulfonamide-phosphonate conjugates as carbonic anhydrase isozymes inhibitors.

The three-components one-pot Kabachnik-Fields reaction of sulfapyridine, diethyl phosphite, and aldehyde under thermal catalysis reaction condition in the presence of bismuth (III) triflate as a catalyst afford the corresponding sulfonamide-phosphonates (3a-3p) in good to excellent yields (78%-91%). The structures of the new synthesized compounds were elucidated and confirmed by variable spectroscopic studies. Single crystal X-ray studies for 3a, 3d, and 3i verified the proposed structure. The newly developed sulfonamide-phosphonates were evaluated for their inhibitory properties against four isoforms of human carbonic anhydrase (hCA I, II, IX, and XII). The results demonstrated that they exhibited greater potency in inhibiting hCA XII compared to hCA I, II, and IX, with Ki ranging from 5.1 to 51.1 nM. Compounds 3l and 3p displayed the highest potency, exhibiting selectivity ratios of I/XII >298.7 and 8.5, and II/XII ratios of 678.1 and 142.1, respectively. Molecular docking studies were conducted to explore their binding patterns within the binding pocket of CA XII. The results revealed that the sulfonamide NH group coordinated with the Zn2+ ion, and hydrogen bond interactions were observed with residue Thr200. Additionally, hydrophobic interactions were identified between the benzenesulfonamide phenyl ring and Leu198. Compounds 3p and 3l exhibited an additional hydrogen bonding interaction with other amino acid residues. These supplementary interactions may contribute to the enhanced potency and selectivity of these compounds toward the CA XII isoform.

Synthesis and Characterization of Novel 2-(1,2,3-Triazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazoles and 2-(4,5-Dihydro-1H-pyrazol-1-yl)-4-(1H-1,2,3-triazol-4-yl)thiazoles.

Reactions of 1-(5-methyl)-1H-1,2,3-triazol-4-yl)ethan-1-ones and benzaldehydes in ethanol under basic conditions gave the corresponding chalcones. Reactions of the chalcones combined with thiosemicarbazide in dry ethanol containing sodium hydroxide afforded the corresponding pyrazolin-N-thioamides. Reactions of the synthesized pyrazolin-N-thioamides and several ketones (namely, ethyl 2-chloro-3-oxobutanoate, 2-bromoacetylbenzofuran, and hydrazonoyl chloride) gave the corresponding novel 2-(1,2,3-triazol-4-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazoles in high yields (77-90%). Additionally, 2-(4,5-dihydro-1H-pyrazol-1-yl)-4-(1H-1,2,3-triazol-4-yl)thiazoles were obtained in high yields (84-87%) from reactions with N-pyrazoline-thioamides and 4-bromoacetyl-1,2,3-triazoles under basic conditions. The structures of six of the newly synthesized heterocycles were confirmed by X-ray crystallography.

Phonatory function and characteristics of voice in recovering COVID-19 survivors.

INTRODUCTION: This study aimed to evaluate the phonatory function of recovered COVID-19 survivors. The universal outbreak of COVID-19 led to the occurrence of otolaryngological manifestations that raised concerns about the assessment of the phonatory function in recovering patients. METHODS: This is a prospective, cross-sectional, case-controlled study carried out on 364 laboratory-confirmed non-critical COVID-19 survivors and 100 as healthy controls. The study participants were classified into two groups according to the disease severity. Group1 comprised 212 survivors who recovered from pneumonia and group 2 was made up of 152 survivors of severe pneumonia. All patients were subjected to an auditory perceptual assessment of the voice (APA) and Maximum Phonation Time (MPT) measurements. RESULTS: Phonasthenic manifestations were significantly more frequent in COVID-19 survivors than in controls (P < 0.000) with a higher percentage recorded among severe pneumonia survivors (87.5%) than among pneumonia survivors (60.8%) with a P value of < 0.01. Dysphonia and excessively soft loudness were significantly more common among survivors than among controls (P < 0.002 and P < 0.000, respectively) with no significant difference between the patient groups. The MPT was significantly shorter among survivors than among controls (P < 0.000). The mean MPT was 15.97 s in the control group, 10.72 s in the pneumonia group, and 8.88 s in the severe pneumonia group, with the differences between the groups being statistically significant (P < 0.000), suggesting a higher impairment of lung volume and phonatory function in severe cases. CONCLUSIONS: Phonasthenia, dysphonia, and decreased MPT could be otolaryngological manifestations of COVID-19. Laryngeal function assessment should be considered in COVID-19 survivors.

Novel allyl-hydrazones including 2,4-dinitrophenyl and 1,2,3-triazole moieties as optical sensor for ammonia and chromium ions in water.

It is critical to take safety action if carcinogenic heavy metals and ammonia can be detected quickly, cheaply, and selectively in an environmental sample. As a result, compound 4a [4-(1-(2-(2,4-Dinitrophenyl)hydrazineylidene)-3-(naphthalen-2-yl)allyl)-5-methyl-1-phenyl-1 H-1,2,3-triazole] and compound 4b [4-(1-(2-(2,4-Dinitrophenyl)hydrazineylidene)-3-(naphthalen-2-yl)allyl)-1-(4-fluorophenyl)-5-methyl-1 H-1,2,3-triazole] were prepared. The aldol condensation process of 4-acetyl-1,2,3-triazoles 1a,b (Ar = C6H4; 4-FC6H4) with 2-naphthaldehyde yields 1-acetyl-1,2,3-triazoles 1a,b (Ar = C6H4; 4-FC6H4) (5-methyl-1-aryl-1 H-1,2,3-triazol-4-yl) -3-(naphthalen-2-yl)prop-2-en-1-ones 3a,b with a yield of around 95%. The target compounds 4a,b are obtained in around 88% yield by condensation of 3a,b with (2,4-dinitrophenyl)hydrazine in a refluxing acidic medium. Compounds 4a,b exhibited possible colorimetric detection for chromium ion in the range of 0-14 ppm and ammonia in the range of 0-20 ppm. As a result, this research suggests that strong electron-withdraw groups in related probes can improve anion detection ability, while the conjugation effect should also be considered while building structures.

Egyptian patients'/guardians' experiences and perception about clinical informed consent and its purpose: Cross sectional study.

BACKGROUND: Informed consent (IC) is a healthcare standard emphasizing the meaning of human dignity as clarified in the Universal Declaration of Human Rights. Data about IC practices in Egypt is insufficient. This study aimed to assess the Egyptian patients'/guardians' experiences about IC and their expectations about its practices' purposes in general and according to the type of the healthcare facility. METHODS: Self-administered questionnaire was carried out for 1092 participants who had undergone or were scheduled to a procedure requiring an IC at three studied types for Egyptian health care facilities. Ten statements were ranked twice by the participants to reflect their perception of IC purpose as per what is currently practiced and what they believe should be practiced. RESULTS: IC implementation varies significantly (p<0.05) across the health care facilities in Egypt. The percentage of its implementation at the non-governmental facilities, governmental facilities, and university hospital was 85.9%, 77.8%, and 63.8 respectively. The first three ranked purposes of the current IC practices were: "Helping patient/guardian decide (64.9%)", "Documenting patient's/guardian's decision (59.3%)", and "Having shared decision (57.3%)". The perceived purposes of IC to be practiced were: "Informing the patient/guardian (68.4%)", "Making sure patient/guardian understand (65.3%)" and "Documenting patients/guardians decisions (65.1%)". "Being a meaningless routine" was reported by the majority to be ranked as a low purpose for IC current and preferred practices. CONCLUSION: The practice of IC is common within the Egyptian medical community. Participants believe that information disclosure "Making sure patients understand" has to help in IC decision making and its main purpose. However, unfortunately, this is not perceived as a current purpose of IC. There was consensus agreement that documenting the patient's/guardian's decision and informing the patient/guardian are perceived as both important current and preferred purposes for IC practices.

Egyptians' social acceptance and consenting options for posthumous organ donation; a cross sectional study.

BACKGROUND: Organ donation has become one of the most effective ways to save lives and improve the quality of life for patients with end-stage organ failure. No previous studies have investigated the preferences for the different consenting options for organ donation in Egypt. This study aims to assess Egyptians' preferences regarding consenting options for posthumous organ donation, and measure their awareness and acceptance of the Egyptian law articles regulating organ donation. METHODS: A cross sectional study was conducted among 2743 participants over two years. Each participant was required to rank eleven consenting options from 1 (most preferred) to 11 (least preferred), and to report his awareness and acceptance of the seven articles of the Egyptian law of organ donation. RESULTS: 47% of the participants expressed willingness to donate their organs after death. This percentage increased to 78% when consenting options were explained to participants. "Informed consent by donor only" was the most preferred type of consent for one third of respondents. Awareness of the law articles regulating organ donation was relatively low ranging from 56% to 23%. CONCLUSION: Currently, around half of the Egyptian population agree to posthumous organ donation. This percentage could be increased significantly by raising the awareness about how the process of donation could be regulated and how the patient's right of decision could be protected.

Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci.

BACKGROUND: The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR) and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs. METHODS: A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007-2008 and 2009-2010). Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests. RESULTS: Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies) than Galabat (8,202 flies). In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month), and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month) while none of flies were collected in August-October (MBR = 0 bites/person/month). In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month) and September 2010 (N = 1,163, MBR = 6,978 bites/person/month), whereas, none appeared in collection from April to June. There was a significant difference in mean monthly density of S. damnosum s.l. across the two foci in 2007-2008 (df = 3, F = 3.91, P = 0.011). Minimum temperature showed significant correlation with adult flies counts in four areas sampled; the adult counts were increased in Nady village (rs = 0.799) and were decreased in Kalasecal (rs = -0.676), Gumaiza (rs = -0.585), and Hilat Khateir (rs = -0.496). Maximum temperature showed positive correlation with black fly counts only in Galabat focus. Precipitation was significantly correlated with adult flies counts in Nady village, Abu-Hamed, but no significance was found in the rest of the sampled villages in both foci. Hourly-based distribution of black flies showed a unimodal pattern in Abu-Hamed with one peak (10:00-18:00), while a bimodal pattern with two peaks (07:00-10:00) and (14:00-18:00) was exhibited in Galabat. CONCLUSION: Transmission of onchocerciasis in both foci showed marked differences in seasonality, which may be attributed to ecology, microclimate and proximity of breeding sites to collection sites. The seasonal shifts between the two foci might be related to variations in climate zones. This information on black fly vector seasonality, ecology, distribution and biting activity has obvious implications in monitoring transmission levels to guide the national and regional onchocerciasis elimination programs in Sudan.

The impact of Merowe Dam on Simulium hamedense vector of onchocerciasis in Abu Hamed focus - Northern Sudan.

BACKGROUND: Abu Hamed, the northernmost onchocerciasis focus in the world, is located along the River Nile banks in the Nubian Desert. Hydroelectric dams can alter activity of black flies and may provide breeding sites for black fly. Merowe Dam, the largest hydropower project in Africa, was built west of Abu Hamed focus in 2009. The impact of the Dam on onchocerciasis and its black fly vectors in Abu Hamed focus was measured in this study. FINDINGS: Entomological surveys for aquatic stages and adult Simulium hamedense were conducted before and after the inception of Merowe Dam in 2007/2008 and 2010/2011. There was no black fly breeding or adult activity in the previously known breeding sites upstream of the Merowe Dam with the western most breeding site found in AlSarsaf village near the center of the focus. No adult or aquatic stages of black flies were found downstream of the Dam. CONCLUSIONS: The artificial lake of the Dam flooded all the breeding sites in the western region of the focus and no aquatic stages and/or adult black fly activity were established in the study area upstream of the Dam. The Dam seems to have positive impact on onchocerciasis and its black fly vectors in Abu Hamed focus. These outcomes of the Merowe Dam might have contributed to the recently declared interruption of onchocerciasis transmission in Abu Hamed focus. Continuous entomological surveys are needed to monitor presence of black fly vectors and its impact on the disease.

Effect of irradiation of wheat grains with fast neutrons on the grain yield and other characteristics of the plants.

The effects of fast neutrons from a (252)Cf source in the fluence range 10(5)-10(8)n/cm(2) on the Egyptian wheat cultivar (Sakha 92) were studied. The experiment was conducted for three successive seasons (2008/2009, 2009/2010, and 2010/2011) to study the effect of the irradiation on the plant growth, grain yield, and physiological changes of three generations of plants produced by irradiated moisturized grains. A low fast-neutron fluence 2 × 10(6)n/cm(2) increased the yield throughout the three mutagenic generations considerably. It also increased concentrations of the total chlorophyll, sugars, and crude protein. These changes improve the quantity and quality of the grain. Also, a study of the effect of salinity of the irrigation water on the characteristics of the third-generation grains produced by neutron-irradiated grains was performed. With increasing concentration of sodium chloride in the irrigation water in the range 0.5-1.5%, concentrations of osmoprotectants, namely, reducing sugars and proline amino acids, increased. The concentration of Na(+) in the grains increased in parallel with the salinity of the irrigation water regardless of irradiation, while the concentrations of Ca(2+) and K(+) decreased.

(2E)-3-(4-Fluoro-phen-yl)-1-[5-methyl-1-(4-methyl-phen-yl)-1H-1,2,3-triazol-4-yl]prop-2-en-1-one.

With respect to the triazole ring in the title compound, C19H16FN3O, the p-tolyl ring is inclined [dihedral angle = 51.79 (11)°], whereas the chalcone residue is almost coplanar [O-C-C-N and C-C-C-C torsion angles = -178.71 (19) and 178.42 (18)°, respectively]. The conformation about the C=C bond [1.328 (3) Å] is E, and the triazole methyl group and the carbonyl O atom are syn. In the crystal, centrosymmetrically related mol-ecules are connected by π-π inter-actions between the triazole and p-tolyl rings [centroid-centroid distance = 3.6599 (12) Å] and these are linked into a three-dimensional architecture by C-H⋯N and C-H⋯π inter-actions.

2-[3-(4-Bromo-phenyl)-5-(4-fluoro-phenyl)-4,5-di-hydro-1H-pyrazol-1-yl]-4-phenyl-1,3-thia-zole.

In the title compound, C24H17BrFN3S, the pyrazole ring is almost planar (r.m.s. deviation = 0.043 Å), with all but the perpendicular fluoro-benzene ring substituents [dihedral angle = 77.9 (3)°] being very approximately coplanar [dihedral angle with the 2-thienyl ring = 19.4 (3)° and with the bromo-benzene ring = 20.3 (3)°; dihedral angle between the 2-thienyl and attached phenyl ring = 11.0 (4)°], so that the mol-ecule has a T-shape. In the crystal, supra-molecular chains along the b-axis direction are sustained by C-H⋯S and C-Br⋯π inter-actions.

5-Methyl-N'-[(3Z)-2-oxo-2,3-dihydro-1H-indol-3-yl-idene]-1-phenyl-1H-1,2,3-triazole-4-carbohydrazide.

In the title compound, C18H14N6O2, the benzene ring is slightly twisted out of the plane of the 1,2,3-triazole ring (r.m.s. deviation = 0.010 Å), forming a dihedral angle of 6.20 (13)°. The nine non-H ring atoms of the fused five- and six-membered ring system are almost coplanar (r.m.s. deviation = 0.032 Å). The near coplanarity in the central residue is consolidated by an intra-molecular bifurcated N-H⋯(O,N) hydrogen bond. The conformation about the N=C bond is Z. In the crystal, supra-molecular chains along [101] are sustained by N-H⋯O hydrogen bonds and C-H⋯O inter-actions. These are consolidated into a three-dimensional architecture by C-H⋯π and π-π inter-actions; the latter occur between centrosymmetrically related 1,2,3-triazole rings [centroid-centroid distance = 3.6056 (14) Å].

Interruption of Onchocerca volvulus transmission in the Abu Hamed focus, Sudan.

Abu Hamed, Sudan, the northernmost location of onchocerciasis in the world, began community-directed treatment with ivermectin (CDTI) in 1998, with annual treatments enhanced to semiannual in 2007. We assessed the status of the parasite transmission in 2011 entomologically, parasitologically, and serologically. O-150 pool screening showed no parasite DNA in 17,537 black flies collected in 2011 (95% confidence interval upper limit [95% CI UL] = 0.023). Skin microfilariae, nodules, and signs of skin disease were absent in 536 individuals in seven local communities. Similarly, no evidence of Onchocerca volvulus Ov16 antibodies was found in 6,756 school children ≤ 10 years (95% CI UL = 0.03%). Because this assessment of the focus meets the 2001 World Health Organization (WHO) criteria for interrupted transmission, treatment was halted in 2012, and a post-treatment surveillance period was initiated in anticipation of declaration of disease elimination in this area. We provide the first evidence in East Africa that long-term CDTI alone can interrupt transmission of onchocerciasis.

2-(2,4-Dichloro-phen-oxy-meth-yl)-5-(4-methyl-phen-yl)imidazo[2,1-b][1,3,4]thia-diazole.

In the title compound, C18H13Cl2N3OS, the eight atoms comprising the central imidazo/thia-diazo-lethia-diazole residue are coplanar (r.m.s. deviation = 0.009 Å). The dihedral angle of 8.72 (13)° between the dichloro-benzene and tolyl rings reflects a twist about the O-C(benzene) bond; the Cm-O-Cb-Cb torsion angle = -168.5 (2)° (m = methyl-ene C and b is benzene C). Supra-molecular tapes along the b axis are found in the crystal structure which are mediated by π-π inter-actions occurring between centrosymmetrically related thia-diazole rings [inter-ring centroid distance = 3.6907 (16) Å] and between the benzene and tolyl rings [inter-ring centroid distance = 3.7597 (16) Å].

5-(4-Fluoro-phen-yl)-3-(4-methyl-phen-yl)-4,5-dihydro-1H-pyrazole-1-carbothio-amide.

The central pyrazole ring in the title compound, C17H16FN3S, adopts an envelope conformation with the methine C atom bearing the 4-fluoro-phenyl substituent as the flap atom. Whereas the tolyl ring is slightly twisted out of the least-squares plane through the pyrazole ring [dihedral angle = 13.51 (11)°], the fluoro-benzene ring is almost perpendicular [dihedral angle = 80.21 (11)°]. The thio-amide group is almost coplanar with the N-N bond of the ring [N-N-C-N torsion angle = 1.2 (3)°] and the amine group forms an intra-molecular hydrogen bond with a ring N atom. In the crystal, supra-molecular double layers in the bc plane are formed via N-H⋯S, N-H⋯F and C-H⋯F inter-actions.

2-[5-(4-Fluoro-phen-yl)-3-(4-methyl-phen-yl)-4,5-dihydro-1H-pyrazol-1-yl]-4-phenyl-1,3-thia-zole.

In the title compound, C25H20FN3S, two independent mol-ecules comprise the asymmetric unit, which differ in the relative orientation of the fluoro-benzene ring with respect to the pyrazole ring to which it is attached [dihedral angles = 89.39 (17) and 75.23 (16)° in the two mol-ecules]. Each pyrazole ring adopts an envelope conformation with the methine C atom being the flap atom. There are additional twists in the mol-ecules, e.g. between the five-membered rings [dihedral angles = 18.23 (16) and 17.84 (16)°] and between the thia-zole and attached phenyl ring [10.26 (16) and 20.87 (15)°]. Overall, each mol-ecule has a T-shape. In the crystal, mol-ecules are connected into a three-dimensional architecture by weak C-H⋯π inter-actions.

3-(4-Chloro-phen-yl)-5-(4-fluoro-phen-yl)-4,5-dihydro-1H-pyrazole-1-carbothio-amide.

In the title compound, C16H13ClFN3S, the pyrazole ring adopts an envelope conformation with the methine C atom being the flap atom. The chloro- and fluoro-benzene rings are twisted out of the plane of the pyrazole ring [dihedral angles = 15.12 (11) and 80.55 (10)°, respectively]. The amine group is orientated towards a ring N atom, forming an intra-molecular N-H⋯N hydrogen bond. This H atom also forms a hydrogen bond to the F atom, which along with N-H⋯S hydrogen bonding leads to a supra-molecular chain along the c axis. Connections between chains of the type Cl⋯π lead to a layer in the bc plane.

4-Dimethyl-amino-1-(4-meth-oxy-phen-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-3-carbonitrile.

In the title compound, C14H13N3O3, a twist occurs, as seen in the dihedral angle of 53.60 (12)° between the pyrrole and benzene rings. A three-dimensional architecture is formed in the crystal whereby layers of mol-ecules in the ac plane are connected by C-H⋯O and C-H⋯π inter-actions.

Novel Antimicrobial Agents: Fluorinated 2-(3-(Benzofuran-2-yl) pyrazol-1-yl)thiazoles.

A new series of 2-pyrazolin-1-ylthiazoles 8a-d and 13-16 was synthesized by cyclization of N-thiocarboxamide-2-pyrazoline with different haloketones and 2,3-dichloroquinoxaline. The structures of the new compounds were confirmed by elemental analyses as well as NMR, IR, and mass spectral data. The newly synthesized compounds were evaluated for their antimicrobial activities, and also their minimum inhibitory concentration (MIC) against most of test organisms was performed. Amongst the tested ones, compound 8c displayed excellent antimicrobial activity.

3-[5-Methyl-1-(4-methyl-phen-yl)-1H-1,2,3-triazol-4-yl]-N-phenyl-5-[4-(piperidin-1-yl)phen-yl]-4,5-dihydro-1H-pyrazole-1-carbothio-amide dimethyl-formamide hemisolvate.

The essentially planar pyrazole ring (r.m.s. deviation = 0.013 Å) in the title hemisolvate, C(31)H(33)N(7)S·0.5C(3)H(7)NO, is almost coplanar with the pendant thio-urea residue [N-N-C-S torsion angle = -173.2 (4)°] and slightly twisted with respect to the triazole ring [dihedral angle = 7.7 (3)°]. An intra-molecular thio-urea-pyrazole N-H⋯N hydrogen bond, via an S(5) loop, is formed. Supra-molecular chains along the c axis are formed in the crystal via piperidine-triazole C-H⋯N inter-actions. These are bridged into loosely associated double chains via C-H⋯O inter-actions involving the disordered (over two positions) dimethyl-formamide solvent mol-ecules. The thio-urea-bound phenyl ring is also disordered over two positions of equal occupancy.