Achour Seridi

The aim of this study was to estimate both the number and annual incidences of human cutaneous leishmaniasis in Algeria over a ten-year period (2010–2019). A retrospective study was conducted using data from all clinically officially notified cases reported between 2010 and 2019. These cases were obtained from the annual reports of the National Institute of Public Health, Algeria. The study showed that 93,838 cases of human cutaneous leishmaniasis were recorded in Algeria. M’Sila reported the highest number of cutaneous leishmaniasis cases during this period (28,836), followed by Biskra (20,549). In contrast, the lowest numbers of cases were registered in Mostaganem (2). Cutaneous leishmaniasis cases were recorded in all 48 provinces of Algeria. The highest number of cutaneous leishmaniasis cases was recorded in 2010, totaling 21,052. However, the lowest number of cases was reported in 2012, with only 57 cases. The peak annual incidence rate, 59.77 per 100,000 humans was recorded in 2010. In the same year, Biskra had the highest annual incidence rate of human cutaneous leishmaniasis (817.17). Conversely, the lowest annual incidence rate was recorded in 2012, at 0.16 per 100,000 humans. In 2010, 2011, 2013, and 2014, Biskra registered the highest annual incidence rates, with 817.17, 540.99, 289.65, and 141.39 per 100,000 humans, respectively. Cutaneous leishmaniasis is endemic in many provinces of Algeria. To our knowledge, this is the first retrospective study of cutaneous leishmaniasis covering all 48 provinces of Algeria during the period 2010–2019.

In this work, two classes of Carbonic Anhydrase (CA) inhibitors, sulfonamide and coumarin derivatives linked to pyta moiety (2a-b) and their corresponding rhenium complexes (3a-b), were designed. These compounds were synthesized and fully characterized by classical analytical methods and X-ray diffraction. All the synthesized compounds were evaluated for their inhibitory activity against the hCA isoforms I, II, IX and XII. They exhibited high inhibitory activities in the range of nanomolar for both hCA IX and hCA XII isoforms. The sulfonamide compound 2a showed the strongest inhibition against the tumour-associated hCA IX isoform with a Ki of 11.7 nM. The tumour-associated isoforms hCA IX and hCA XII were selectively inhibited by all the coumarin derivatives, with inhibition constants ranging from 12.7 nM (2b) to 44.5 nM (3b), while the hCA I and II isoforms were slightly inhibited (in the micromolar range), as expected. In terms of selectivity, compared to previously published rhenium complex-based CA inhibitors, complex 3b showed one of the highest selectivities against hCA IX and hCA XII compared to the off-target isoforms hCA I and hCA II, making it a potential anti-cancer drug candidate. Molecular docking calculations were performed to investigate the inhibition profiles of the investigated compounds at the tumour-associated hCA IX active site and to rationalize our results.

In this work, two bidentate 2-pyridyl-1,2,3-triazole ligands (3a and 3b) containing a 4-substituted benzenesulfonamide pharmacophore prepared by classical click chemistry procedures, as well as their corresponding rhenium complexes, 4a and 4b of general formula [ReCl(CO)₃(L)] (L = 3a or 3b) were prepared and fully characterised by spectroscopic methods (IR, NMR, MS, UV-Vis), elemental analysis, X-ray diffraction, and theoretical studies using DFT and TD-DFT methods. In particular, we showed that, in the solid state, the pyridine and the triazole rings of 3b adopted an uncommon cis configuration which stems from intermolecular hydrogen bonds. Preliminary assays demonstrated a promising nanomolar inhibitory activity against carbonic anhydrase isoform IX for both ligands and complexes with a strong affinity K_i of 2.8 nM for ligand 3a. More interestingly, complex 4b exhibited a pronounced selectivity against hCA IX over the off-targets hCA I and hCA II which makes this compound a promising potential anticancer drug candidate.

The charge transfer complexes of the donor 4-isopropyl-2-benzyl-1,2,5-thiadiazolidin-3-one1,1-dioxide (SF) with π acceptors 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and tetracyanoethylene (TCNE) have been studied spectrophotometrically in chloroform and methanol at room temperature. The results indicated the formation of CT-complexes with a molar ratio of 1 : 1 between donor and each acceptor. The physical parameters of the CT-complexes were evaluated using the Benesi–Hildebrand equation. The data were analyzed in terms of their stability constant (K), molar extinction coefficient (ε_CT), thermodynamic standard reaction quantities (ΔG⁰, ΔH⁰, ΔS⁰), oscillator strength (f), transition dipole moment (μ_EN) and ionization potential (I_D). The experimental studies were complemented by quantum chemical calculations by the time-dependent density functional theory (TD-DFT) at the B3LYP level. The theoretical UV visible and FT-IR spectra were compared with those obtained experimentally. The first order hyperpolarizability (β₀) and related properties (α₀ and Δα) are calculated using the B3LYP method on the finite-field approach. The Mulliken charges, MEP calculations, the electronic properties, HOMO and LUMO energies and NBO analysis were performed on an optimized charge transfer complex of SF-DDQ.

Three new pyridyltriazole ligands (named pyta) bearing a 4-substituted phenyl arm (nitro- (2a), chloro- (2b) or aminophenyl (2c) moiety) have been synthesized using a convenient click chemistry strategy. The corresponding tricarbonylrhenium complexes 3a, 3b and 3c were prepared and fully characterized by means of NMR, IR and mass spectrometry, as well as X-ray crystallography for two of them (3a and 3b). The direct connection of a 4-substituted phenyl arm at the N1 position of the triazolyl ring has a significant influence on the geometry of both, the ligands and their corresponding Re-complexes. The dominant structural feature of these complexes concerns the crystal cohesion. Slip-stacked π–π interactions between two molecules of the complex were observed for 3a and 3b probably resulting from the co-planarity of the organic framework. Furthermore, a combined experimental study and DFT calculations showed that the nature of the pendant arm (X = NO₂, NH₂ or Cl) could affect the electronic properties of the Re-complexes. If the chloro- or aminophenyl moieties unmodified the photo-physical properties of the complexes 3b and 3c, the presence of a nitrophenyl arm for the complex 3a quenched the luminescence, due to a high probability of non-radiative deactivation.