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The rationale at the basis of targeted approach in oncology is radically shifting—from development of highly specific agents aiming at a single target towards molecules interfering with multiple targets. This study was performed to isolate and characterize bioactive molecules from Olax subscorpioidea stem and investigate their potentials as multi-targeted inhibitors against selected non-small cell lung cancer, breast cancer and chronic myelogenous leukemia oncogenic targets. Three compounds: β-sitosterol (1), α-amyrin (2) and stigmasterol (3) were isolated. The structures of 1 − 3 were elucidated by analysis of their spectroscopic data (NMR, MS and IR). To the best of our knowledge, this is the first time these compounds were isolated from O. subscorpioidea stems. Furthermore, integrated analysis of MS/MS data using the Global Natural Products Social Molecular Networking (GNPS) workflow enabled dereplication and identification of 26 compounds, including alkaloids (remerine, boldine), terpenoids (3-hydroxy-11-ursen-28,13-olide, oleanolic acid), flavonoids (kaempferitrin, olax chalcone A) and saponins in O. subscorpioidea stem. Molecular docking studies revealed that some of the compounds, including olax chalcone A (–9.2 to −10.9 kcal/mol), 3-Hydroxy-11-ursen-28,13-olide (–6.6 to −10.2 kcal/mol), α-amyrin (–6.6 to −10.2 kcal/mol), stigmasterol (–7.7 to −10.1 kcal/mol), β-Sitosterol (–7 to −9.9 kcal/mol) and kaempferitrin (–7.7 to −9 kcal/mol) possessed good inhibitory potentials against selected cancer targets, when compared with reference inhibitors (–8.4 to −13.7 kcal/mol). A few of these compounds were shown to have considerable to favorable pharmacokinetic and drug-likeness properties. This study provides some rationale for the use of O. subscorpioidea in ethnomedicinal management of cancer and identifies some potential anticancer agents. Communicated by Ramaswamy H. Sarma

In the search for new `sulfa drugs' with therapeutic properties, o-nitrosulfonamides and N-cycloamino-o-sulfanilamides were synthesized and characterized using techniques including 1H NMR, 13C NMR and FT–IR spectroscopy, and single-crystal X-ray diffraction (SC-XRD). The calculated density functional theory (DFT)-optimized geometry of the molecules showed similar conformations to those obtained by SC-XRD. Molecular docking of N-piperidinyl-o-sulfanilamide and N-indolinyl-o-sulfanilamide supports the notion that o-sulfanilamides are able to bind to human carbonic anhydrase II and IX inhibitors (hCA II and IX; PDB entries 4iwz and 5fl4). Hirshfeld surface analyses and DFT studies of three o-nitrosulfonamides {1-[(2-nitrophenyl)sulfonyl]pyrrolidine, C10H12N2O4S, 1, 1-[(2-nitrophenyl)sulfonyl]piperidine, C11H14N2O4S, 2, and 1-[(2-nitrophenyl)sulfonyl]-2,3-dihydro-1H-indole, C14H12N2O4S, 3} and three N-cycloamino-o-sulfanilamides [2-(pyrrolidine-1-sulfonyl)aniline, C10H14N2O2S, 4, 2-(piperidine-1-sulfonyl)aniline, C11H16N2O2S, 5, and 2-(2,3-dihydro-1H-indole-1-sulfonyl)aniline, C14H14N2O2S, 6] suggested that forces such as hydrogen bonding and π–π interactions hold molecules together and further showed that charge transfer could promote bioactivity and the ability to form biological interactions at the piperidinyl and phenyl moieties.

The preparation of cocrystals from active pharmaceutical ingredients (APIs) and biologically relevant coformers offers the opportunity of obtaining compounds with more desirable physicochemical and...

Three new compounds containing mono- and dinuclear Cu(II) complexes, [Cu(Met)2Cl2]2, Cu(H2O)(Met)2Cl]2 and [Cu(H2O)(phen)2]NO3 (Met = metronidazole; Phen = 1,10-phenathroline) have been synthesized and characterized by Infra-Red, UV–Vis, Single Crystal X-ray analyses, Thermogravimetric techniques and Scanning electron micrography. The biological activities of the complexes were evaluated against a series of Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii); Gram-positive (Enterococcus faecium, Bacillus cereus and Staphylococcus aureus) strains as well as the yeasts (Candida albicans and Cryptococcus neoformans). Density-functional theory (DFT) studies revealed that compound [Cu(Met)2Cl2]2 is less stable in comparison to compounds, [Cu(H2O)(phen)2]NO3 and [Cu(H2O)(Met)2Cl]2. Docking studies of Cu(II) complexes with DNA structure (PDB id 1ZEW) found drug activity by groove binding. Binding mode of Cu(II) complexes with (i) fungal cytochrome P450 sterol 14α-demethylase (CYP51), which facilitates the synthesis of ergosterol in fungi; (ii) 4HL2; a New Delhi metallo-β-lactamase-1 (NDM-1) produced by strains of K. pneumoniae and (iii) 4M7U; an enzyme dihydrofolate reductase (DHFR) responsible for E. faecium activity and bacterial growth was established via docking studies. In general, [Cu(Met)2Cl2]2 was the most broad-spectrum antimicrobial compound, indicating an important role of electron-withdrawing substituents such as chlorine and suggest their potential application as antibacterial agents. The findings should be helpful in the development of antimicrobial drugs of Cu(II) complexes of metronidazole and 1,10 phenanthroline.