Crystallography, Molecular Modeling, and COX-2 Inhibition Studies on Indolizine Derivatives

The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a–e) were carried out and evaluated for COX-2 enzyme inhibition. All the compounds showed activity in micromolar ranges, and the compound diethyl 3-(4-cyanobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5a) emerged as a promising COX-2 inhibitor with an IC50 of 5.84 µM, as compared to indomethacin (IC50 = 6.84 µM). The molecular modeling study of indolizines indicated that hydrophobic interactions were the major contribution to COX-2 inhibition. The title compound diethyl 3-(4-bromobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5c) was subjected for single-crystal X-ray studies, Hirshfeld surface analysis, and energy framework calculations. The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 21/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, β = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)Å3. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy

Anesthetic Considerations in the Evaluation of Children with Glaucoma and Associated Conditions

Glaucoma in the pediatric population can be difficult to diagnose and treat without a child’s cooperation. Examination and intervention under anesthesia play a critical role in the management of childhood glaucoma, as detailed elsewhere. This requires a change in setting from the office to the operating room with the availability and assistance of a pediatric anesthesiologist, who may have to sedate or anesthetize the child repeatedly, sometimes even just to confirm the glaucoma diagnosis. An anesthesiologist with specialty training in pediatrics is pertinent, as childhood glaucoma can often be associated with syndromes involving other organ systems, hence making their anesthetic complicated and at times potentially dangerous. Once the glaucoma diagnosis is established, these children may have to return to the operating room multiple times for examinations and/or treatments; thus, having prior anesthetic records with any previous complications can offer vital information to both the pediatric anesthesiologist and pediatric glaucoma specialist. This chapter focuses on the preoperative workup of pediatric patients to ensure that they are optimized medically to undergo sedation and general anesthesia with the lowest possible risk. The intraoperative course is also described, including why sedation may be chosen over general anesthesia and how the various anesthetic drugs such as volatile anesthetics or intravenous induction agents can affect intraocular pressure measurements. The chapter finishes by describing potential postoperative complications related to anesthesia: nausea, vomiting, postoperative delirium, and agitation, along with a brief discussion on various syndromes that could potentially affect the delivery and choice of anesthetic