A comprehensive review of discovery and development of drugs discovered from 2020-2022.

To fully evaluate and define the new drug molecule for its pharmacological characteristics and toxicity profile, pre-clinical and clinical studies are conducted as part of the drug research and development process. The average time required for all drug development processes to finish various regulatory evaluations ranges from 11.4 to 13.5 years, and the expense of drug development is rising quickly. The development in the discovery of newer novel treatments is, however, largely due to the growing need for new medications. Methods to identify Hits and discovery of lead compounds along with pre-clinical studies have advanced, and one example is the introduction of computer-aided drug design (CADD), which has greatly shortened the time needed for the drug to go through the drug discovery phases. The pharmaceutical industry will hopefully be able to address the present and future issues and will continue to produce novel molecular entities (NMEs) to satisfy the expanding unmet medical requirements of the patients as the success rate of the drug development processes is increasing. Several heterocyclic moieties have been developed and tested against many targets and proved to be very effective. In-depth discussion of the drug design approaches of newly found drugs from 2020 to 2022, including their pharmacokinetic and pharmacodynamic profiles and in-vitro and in-vivo assessments, is the main goal of this review. Considering the many stages these drugs are going through in their clinical trials, this investigation is especially pertinent. It should be noted that synthetic strategies are not discussed in this review; instead, they will be in a future publication.

Variations in the frequencies of polymorphisms in the CYP2C9 gene in six major ethnicities of Pakistan.

Genetic variation in cytochrome P450 (CYP) 2C9 is known to cause significant inter-individual differences in drug response and adverse effects. The frequencies of CYP2C9*2 and CYP2C9*3, both of which are responsible for the low activity of the enzyme, are not known in the Pakistani population. Therefore, we screened various ethnic groups residing in Pakistan for these polymorphisms. A total of 467 healthy human volunteers were recruited from six major ethnicities of Pakistan after written informed consent. Our results indicate that about 20% of the Pakistani population has a genotype containing at least one low activity allele. Ethnic Punjabi and Pathan populations had the highest frequencies of wild type genotypes while Urdu, Seraiki, and Sindhi populations showed higher rates of both low activity genotypes. The Baloch population showed the highest rates of low activity genotypes with less than 50% of the samples showing wild type genotypes, suggesting that more than half of the Baloch population possesses low activity genotypes. The frequencies found in various ethnic groups in Pakistan were comparable with ethnicities in the South Asian region except for the Baloch population. These results suggest that pharmacogenetics screening for low activity genotypes may be a helpful tool for clinicians while prescribing medications metabolized by CYP2C9.

Sulfa drugs as inhibitors of carbonic anhydrase: new targets for the old drugs.

Sulfa drugs are well-known antibacterial agents containing N-substituted sulfonamide group on para position of aniline ring (NH2RSO2NHR'). In this study 2,4-dichloro-1,3,5-triazine derivatives of sulfa drugs, sulfamerazine (1b), sulfaquinoxaline (2b), sulfadiazine (3b), sulfadimidine (4b), and sulfachloropyrazine (5b) (1a-5a) were synthesized and characterized. Their carbonic anhydrase inhibition activity was evaluated against bovine cytosolic carbonic anhydrase isozyme II (bCA II). For the sake of comparison the CA inhibition activity of the parent sulfa drugs (1b-5b) was also evaluated. A significant increase in CA inhibition activity of sulfa drugs was observed upon substitution with 2,4-dichloro-1,3,5-triazine moiety. Molecular docking studies were carried out to highlight binding site interactions. ADME properties were calculated to evaluate drug likeness of the compounds.