The drug discovery and development (DDD) process in pursuit of novel drug candidates is a challenging procedure requiring lots of time and resources. Therefore, computer-aided drug design (CADD) me... Plain language summary An extensive survey of technological applications in drug discovery and development, encompassing offline and online approaches, is presented in this review. The span of rese... Tweetable abstract The DDD process in pursuit of novel drug candidates is a challenging procedure requiring lots of time and resources. This article provides an overview of virtual approaches, whic...

Molecular docking is a bioinformatics-based theoretical simulation strategy. It is employed to study ligand-protein interaction profiles and predict their binding conformers and affinity through computational tools. Since the 1980s, computational tools have been used in the drug discovery process. The initial molecular modeling approaches available at the time focused on a rigid view of the ligand-protein interaction due to the limited computational capabilities. The advancement of hardware technology has made it possible to simulate the dynamic character of the ligand-protein interactions throughout time. The current chapter deals with an outline of the progression of structure-based drug discovery methodologies in the investigation of the ligand-protein interaction profiles from static to improved molecular docking strategies.

Aim: Phenanthridines are an essential class of nitrogenous heterocycles with extensive applications in medicinal chemistry. The development of efficient and eco-friendly methods for the preparation... Graphical abstract

Background: Mixed ligand-metal complexes are efficient chelating agents because of their flexible donor ability. Mixed ligand complexes containing hetero atoms sulphur, nitrogen and oxygen have been probed for their biological significance. Methods: Nine mixed ligand-metal complexes of 2-(butan-2-ylidene) hydrazinecarbothioamide (2- butanone thiosemicarbazone) with pyridine, bipyridine and 2-picoline as co-ligands were synthesized with Cu, Co and Zn salts. The complexes were tested against MDA-MB231 (MDA) and A549 cell lines. Antibacterial activity was tested against Staphylococcus aureus and Escherichia coli. The drug character of the complexes was evaluated on parameters viz. physicochemical properties, bioactivity scores, toxicity assessment and Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) profile using various automated softwares. Molecular docking was performed against Ribonucleotide Reductase (RR) and topoisomerase II (topo II). Results: The mixed ligand-metal complexes were synthesized by condensation reaction for 4-5 h. The characterization was done by elemental analysis, 1H-NMR, FT-IR, molar conductance and UV spectroscopic techniques. Molecular docking results showed that [Cu(C₅H₁₁N₃S)(py)2(CH3COO)2], [Zn(C₅H₁₁N₃S)(bpy)(SO₄)] and [Zn(C₅H₁₁N₃S)(2-pic)2(SO4)] displayed the lowest binding energies with respect to RR. Against topo II [Cu(C₅H₁₁N₃S)(py)2(CH3COO)2], [Cu(C₅H₁₁N₃S)(bpy)(CH3COO)2] and [Zn(C₅H₁₁N₃S)(2-pic)2(SO₄)] had the lowest energies. The druglikness assessment was done using Leadlikeness and Lipinski’s rules. Not more than two violations were obtained in case of each filtering rule showing drug-like character of the mixed ligand complexes. Some of the complexes exhibited positive bioactivity scores and almost all the complexes were predicted to be safe with no hazardous effects as predicted by the toxicity assessment. Ames test predicted the non-mutagenic nature of the complexes. Conclusion: In vitro activity evaluation showed that [Zn(C₅H₁₁N₃S)(py)2(SO₄)], [Co(C₅H₁₁N₃S(bpy) (Cl)2] and [Cu(C₅H₁₁N₃S)(2-pic)2(CH3COO)2] were active against MDA. Against A549 [Co(C₅H₁₁N₃S)(py)2(Cl)2], [Cu(C₅H₁₁N₃S)(py)2(CH3COO)2] and [Co(C₅H₁₁N₃S(bpy)(Cl)2] were active. Antibacterial evaluation showed that [Co(C₅H₁₁N₃S)(bpy)(Cl)2], [Zn(C₅H₁₁N₃S)(2-pic)2(SO₄)] and [Cu(C₅H₁₁N₃S)(2-pic)2(CH3COO)2] were active against S. aureus. Against E. coli, [Zn(C₅H₁₁N₃S)(2- pic)2(SO₄)] showed activity at 18-20 mg dose range.