ABSTRACT
In recent years, computational approaches in genomics, proteomics, and structural bioinformatics have explored thousands of drug targets and provided enormous opportunities in the field of drug discovery. The co-integration of computational approaches and experimental techniques is essential for identifying and developing promising molecules for lethal disease, as computational approaches take less time and cost less money than experimental ones. This chapter sheds light on the process of structure-based designing for inflammatory and infectious diseases. This study initially illustrated the steps like target identification, homology modeling, active site prediction/identification, ligand preparation, virtual screening, molecular docking, pharmacophore modeling, molecular dynamics simulation, etc., along with examples of computer-aided drug designing (CADD). Further, it elaborates on the potent candidates against different drug targets like Janus kinase (JAK), Bruton tyrosine kinase (BTK), sphingosine-1-phosphate (S1P), spleen tyrosine kinase (SYK), etc. of inflammatory diseases. Dihydrofuran diamine derivatives were synthesized and screened against multi-target (SYK/PDGFR-α/C-kit) for anti-rheumatoid arthritis. Pyrazole-pyrimidine derivatives were found as basic scaffolds exhibiting an anti-inflammatory activity. Furthermore, key principles and the importance of drug designing will be illustrated by case studies of drug targets like methicillin resistance factor A, protein kinases, lipophilic membrane protein (LLM), GTPase, etc. of infectious diseases. Potent drug candidates (ofloxacin, roflumilast, furazolidone, gemifloxacin, paromomycin, streptomycin, and tobramycin) have been reported against FmtA of Staphylococcus aureus by the use of in silico and experimental approaches. Another methicillin resistance factor, LLM, is screened against antibacterial molecules, and further stability of compounds with LLM was confirmed by molecular dynamics (MD) simulation. Virtual screening and pharmacophore modeling have been utilized to report the potent antimicrobials against YsxC, a GTPase of S. aureus. Potent natural product-like compounds were reported by virtual screening, molecular docking, and MD simulation against FemC.
