New thiazole, thiophene and 2-pyridone compounds incorporating dimethylaniline moiety: synthesis, cytotoxicity, ADME and molecular docking studies.

Various sets of thiazole, thiophene, and 2-pyridone ring structures containing a dimethylaniline component were synthesized. Substituted thiazoles 2-3 and thiophenes 5-7 were produced by reacting thiocarbamoyl compound 4 with α-halogenated reagents in different basic conditions. Also, a series of 2-pyridone derivatives 9a-f substituted with dimethylaniline was synthesized through Michael addition of malononitrile to α,ß-unsaturated nitrile derivatives 8a-f. The synthesized products were structurally proven by spectroscopic methods such as IR, 1H NMR, 13C NMR, and MS data. Furthermore, the anti-cancer efficacy of the compounds was assessed using the MTT assay on two cell lines: hepatocellular carcinoma (HepG-2) and breast cancer (MDA-MB-231). The results showed the highest growth inhibition for derivatives 2, 6, 7, and 9c, which were further examined for their IC50 values. The IC50 for compound 2 showed equipotent activity (IC50 = 1.2 µM) against the HepG-2 cell line compared to Doxorubicin (IC50 = 1.1 µM). Compounds 2, 6, 7 and 9c showed very good ADME assessments for further drug administration. Moreover, the PASS theoretical prediction for the compounds showed high antimitotic and antineoplastic activities for compounds 2, 6, 7, and 9c, as well as potent inhibition activity for the insulysin enzyme (IDE). Molecular docking stimulations were performed on CDK1/CyclinB1/CKS2 (PDB ID: 4y72) and BPTI (PDB ID: 2ra3). When docked into (PDB ID: 4y72), all of the tested compounds showed considerable inhibition, and the 2-pyridone derivative 9d had the maximum binding affinity (- 8.1223 kcal/mol). While thiophene derivative 6 offered the maximum binding affinity (- 7.5094 kcal/mol) when docked into (PDB ID: 2ra3).

Arylidine extensions of 3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-benzenesulfonamide derivatives: Synthesis, computational simulations and biological evaluation as tumor-associated carbonic anhydrase inhibitors.

Several pyrazole-benzene sulfonamides were reported as human carbonic anhydrase inhibitors. In this research work, a design of Arylidine-extented 5-oxo-pyrazole benzenesulfonamides (4a-i), (8a-d) and (10a-e) were reported based on tail-approach design. Beside the reported synthetic procedures and confirmation by different analytical procedures, a DFT study was employed to confirm the Z- conformer of the synthesized compounds. In vitro biological assay against four different human carbonic anhydrases took place and based on the results, SAR study was illustrated and selectivity indexes were discussed. Compounds 4g and 8a exhibited the best inhibitory activity among the target compounds with values (hCAIX: KI = 71.2 nM, hCAXII: KI = 22.5 nM), (hCAIX: KI = 34.3 nM, hCAXII: KI = 74.3 nM); respectively. Both of them were subjected to cellular assay against two different cancer cell lines with expressing nature to hCA isoforms under both normoxic and hypoxic conditions. Compound 4g showed the highest cytotoxic activity against MCF-7 cancer cell line (IC50 = 4.15 µM under hypoxic conditions and IC50 = 8.59 µM under normoxic conditions) compared to the reference drug doxorubicin under normoxic, (IC50 = 4.34 µM), and hypoxic, (IC50 = 2.23 µM), conditions. Further cellular investigations were employed to study the effect of this compound on the cell cycle of the affected cell line. Finally, molecular docking supported by molecular dynamic simulation was utilized to understand the mechanism of the inhibitory activity of two of these compounds - as representative examples- based on the designed rational.

Synthesis, DFT investigations, antioxidant, antibacterial activity and SAR-study of novel thiophene-2-carboxamide derivatives.

Synthetic strategy for the synthesis of thiophene 2-carboxamide derivatives substituted with hydroxyl, methyl and amino groups at position-3 was proposed. The strategy includes the cyclization of the precursor ethyl 2-arylazo-3-mercapto-3-(phenylamino)acrylate derivatives, 2-acetyl-2-arylazo-thioacetanilide derivatives and N-aryl-2-cyano-3-mercapto-3-(phenylamino)acrylamide derivatives with N-(4-acetylphenyl)-2-chloroacetamide in alcoholic sodium ethoxide. IR, 1H NMR, and mass spectroscopic analyses were used to characterize the synthesized derivatives. In addition, molecular, electronic properties of the synthesized products were studied by the density functional theory (DFT) where they exhibited close HOMO-LUMO energy gap (ΔEH-L) in which the amino derivatives 7a-c have the highest while the methyl derivatives 5a-c were the lowest. Using the ABTS method, the antioxidant properties of the produced compounds were evaluated, where amino thiophene-2-carboxamide 7a exhibit significant inhibition activity 62.0% compared to ascorbic acid The antibacterial activity against two pathogenic Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two of pathogenic Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) revealed that 7b records the highest activity index compared to ampicillin 83.3, 82.6, 64.0, 86.9%, respectively. Furthermore, the thiophene-2-carboxamide derivatives were docked with five different proteins with the use molecular docking tools and the results explained interactions between amino acid residue of enzyme and compounds. Compounds 3b and 3c showed the highest binding score with 2AS1 protein.

Tailoring Screening Guidelines for Retinopathy of Prematurity in Egypt: An Exploratory Multicentric Study.

Background: Retinopathy of prematurity (ROP) is increasing in incidence in developing nations, including Egypt. Secondary prevention requires timely detection through the development of regional screening guidelines, which should be preceded by large-scale studies to characterize the population at risk. Methods: A prospective, multicentric exploratory study that included five large tertiary institutions in an urban Egyptian setting. All infants born with gestational age (GA) < 37 weeks and/or birth weight (BW) ≤ 2000 grams were screened. More mature and heavier infants with unstable clinical course were also included. The primary outcome measure was the rate of ROP and high-risk disease occurrence in relation to underlying risk factors. Results: Of the 768 eyes (384 screened infants), 347 eyes (45.2%) had stage 1 or higher disease, and 43 eyes (5.6%) had high-risk disease. Eyes with stage 1 or higher ROP and treatment-requiring ROP had a mean (± SD) GA of 33.4 (± 2.6) weeks and 32.8 (± 3.2) weeks, and BW of 1842.3 (± 570.1) grams and 1747.6 ± (676.2) grams, respectively. Treatment-requiring eyes belonged to infants that had significantly lower GA and significantly higher prevalence of co-morbidities than non-treatment-requiring eyes. Conclusion: The incidence of ROP and high-risk disease in an urban Egyptian setting are similar to those in comparable settings elsewhere and locally. This exploratory study supports tailoring local screening criteria for ROP, and may aid the future development of national guidelines.

Visual performance following implantation of presbyopia correcting intraocular lenses.

OBJECTIVE: To compare the visual outcomes following bilateral implantation of 3 presbyopia correcting IOLs. METHODS: Results are reported for patients who underwent phacoemulsification with bilateral implantation of one of the following IOLs: Panoptix IOL, AT LISA tri IOL and Symphony IOL. Six months postoperative examination included monocular UIVA at 80 and 60 cm and monocular UNVA and DCNVA at 40 cm, monocular UDVA and CDVA, Spherical equivalent (SE) refraction, binocular defocus curve, contrast sensitivity, photopic phenomena, and spectacle independence. RESULTS: UIVA at 80 cm was significantly better in the AT LISA group and the Symfony groups than the Panoptix group, while UIVA at 60 cm was better in the Symfony group and the Panoptix group than the AT LISA group. A worse DCNVA was recorded in the Symfony group. At a defocus of -2.50 D, the near VA was similar in the PanOptix and AT LISA groups (0.05, 0.07 logMAR respectively), which were significantly better than the Symfony group (0.3 LogMAR). Binocular photopic and scotopic contrast sensitivity outcomes were similar among the three groups at all spatial frequencies. In Symphony group, the frequency and the degree of bother of photic phenomena was relatively higher than the other two groups. Higher percentage of patients in symphony group reported their need for reading glasses. CONCLUSION: PanOptix IOL and AT LISA IOL would be a good choice for patients aiming for an optimum near vision, while Symfony IOL seems suitable for patients having the priority for good intermediate vision.

Retro-equatorial inferior oblique myopexy for treatment of inferior oblique overaction.

AIM: To compare the effectiveness of inferior oblique retroequatorial myopexy and inferior oblique myectomy in correction of inferior oblique overaction (IOOA). PATIENTS AND METHODS: This was a pilot study study including forty patients with primary IOOA of all grades, with or without primary position horizontal deviations. Patients were randomized to have either IO retroequatorial myopexy, group A, or IO myectomy, group B. Success was defined as elimination of the IOOA at 6 months postoperatively. Secondary outcome measures included residual or recurrent elevation in adduction, development of postoperative hypotropia in adduction, postoperative contralateral IOOA, major intraoperative complications, and reversibility of the procedure. RESULTS: At 6 months postoperative, the success rate was higher in the myectomy group (76%) than in the myopexy group (58%); however, this difference was not statistically significant (P = 0.1). The incidence of residual IOOA in myopexy group was significantly higher in patients with higher preoperative grades of IOOA (P Ë‚ 0.001). While this difference was not statistically significant among patients in myectomy group (P = 0.09). Collapse of V-pattern was acheived in nine (69%) patients in myopexy group compared with 8 (57%) in myectomy group with a statistically significant difference (P ≤ 0.001). No patients in myopexy group developed postoperative hypotropia in adduction or postoperative contralateral IOOA, compared with eight (22%) patients of myectomy group (P = 0.002) who developed postoperative hypotropia and two (66.6%) patients with unilateral IOOA who developed contralateral IOOA in myectomy group (P Ë‚ 0.001). No intraoperative complications were encountered in either group. postoperative. CONCLUSIONS: Retroequatorial myopexy of the inferior oblique is as effective as inferior oblique myectomy in eliminating lower and moderate grades of primary IOOA; however, it is more effective in collapsing V-pattern associated with IOOA, and is not associated with postoperative hypotropia or contralateral IOOA after unilateral surgery. It can be used as a safe, reversible alternative to myectomy; however, it is not suitable for high grades of IOOA.