Coupling of acceptor-substituted diazo compounds and tertiary thioamides: synthesis of enamino carbonyl compounds and their pharmacological evaluation

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides. We plan to use this method to synthesize indolizidine (−)-237D analogs to find α6-selective antismoking agents. Therefore, we also performed in silico α6-nAchRs binding studies of selected products. Compounds with low root-mean-square deviation values showed more favorable binding free energies. We also report preliminary pharmacokinetic data on indolizidine (−)-237D and found it to have weak activity at CYP3A4. In addition, as enamino carbonyl compounds are also known for antimicrobial properties, we screened previously reported and new enamino carbonyl compounds for antibacterial, antimicrobial, and antifungal properties. Eleven compounds showed significant antimicrobial activities.

This paper describes the synthesis of enamino carbonyl compounds by the copper(i)-catalyzed coupling of acceptor-substituted diazo compounds and tertiary thioamides.     

Rare non‐syndromic bilateral maxillary and mandibular permanent canine agenesis

Oligodontia or absence of teeth such as the Canines is rare and is often accompanied with several other missing teeth. This condition may also be accompanied with morphological and growth related changes in the teeth and the maxillofacial complex. Complete agenesis of the permanent canines in the maxilla and the mandible is extremely rare and occurs in association with syndromic oligodontia. Non‐syndromic absence of canines however, is extremely rare and has only been reported twice. Studies have shown that the incidence of missing canines is more in females. This report describes a sporadic case of congenital absence of maxillary and mandibular bilateral canines. The patient reported to the clinic with a chief complaint of crowding and wanted alignment. On intra‐oral examination it was observed that the patient had all permanent canines missing with no prior history of extractions, crowding in both the arches and class I molars on both sides. With no other symptoms fixed orthodontic therapy was planned for the patient with premolars substituted for the canines.     

Vogt Koyanagi Harada disease following a recent COVID-19 infection

A 23-year-old female presented with a 3-day history of bilateral (OU) diminution of vision 3 weeks after COVID-19 infection. Best corrected visual acuity (BCVA) was 20/30 in right eye and 20/40 in left eye. Anterior segment showed OU 1+ cells in anterior chamber and anterior vitreous face. Fundus OU showed disc hyperemia and multiple pockets of subretinal fluid (SRF), confirmed on optical coherence tomography. Fundus fluorescein angiography showed multiple pin point leaks suggestive of Vogt Koyanagi Harada disease. Oral corticosteroids 1 mg/kg/day were started. At 2-months’ follow-up, her BCVA improved to 20/25 OU with complete resolution of SRF.     

A Current Review of Cypermethrin-Induced Neurotoxicity and Nigrostriatal Dopaminergic Neurodegeneration

Cypermethrin, a class II pyrethroid pesticide, is used to control insects in the household and agricultural fields. Despite beneficial roles, its uncontrolled and repetitive applications lead to unintended effects in non-target organisms. Cypermethrin crosses the blood-brain barrier and induces neurotoxicity and motor deficits. Cypermethrin prolongs the opening of sodium channel, a major site of its action, leading to hyper-excitation of the central nervous system. In addition to sodium channel, cypermethrin modulates chloride, voltage-gated calcium and potassium channels, alters the activity of glutamate and acetylcholine receptors and adenosine triphosphatases and induces DNA damage and oxidative stress in the neuronal cells. Cypermethrin also modulates the level of neurotransmitters, including gamma-aminobutyric acid and dopamine. It is one of the most commonly used pesticides in neurotoxicology research not only because of its variable responses depending upon the doses, time and routes of exposure and strain, age, gender and species of animals used across multiple studies but also owing to its ability to induce the nigrostriatal dopaminergic neurodegeneration. This article describes the effect of acute, chronic, developmental and adulthood exposures to cypermethrin in experimental animals. The article sheds light on cypermethrin-induced changes in the central nervous system, including its contribution in the onset of specific features, which are associated with the nigrostriatal dopaminergic neurodegeneration. Resemblances and dissimilarities of cypermethrin-induced nigrostriatal dopaminergic neurodegeneration with sporadic and chemicals-induced disease models along with its advantages and pitfalls are also discussed.