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Arene metal precursors on treatment with thiosemicarbazone ligands (L1, L2, and L3) yielded a series of cationic mono- and binuclear complexes (1–9) with N∩S bonding mode. In general, the complexes have been formulated as [(p-cymene)Ru(L)Cl]+ and [Cp*2M2(L)2]4+ where L = L1, L2, L3, M = Rh/Ir. Contrary to previous results [1], ruthenium complexes portrayed mononuclear bidentate chelation while rhodium and iridium complexes revealed dinuclear bridging coordination through sulfur and imine nitrogen atoms. All these complexes have been characterized by various spectroscopic techniques and antibacterial studies have been carried out for the complexes as well as the ligands, where 5 and 8 showed good inhibitory antibacterial activity.

Complexes 1–9 were prepared by the reaction of [(arene)MCl2]2 (arene = p-cymene, Cp*; M = Ru, Rh and Ir) with thiourea derivative ligands L1, L2 and L3. These complexes have been isolated as cationic bidentate (N, S), neutral bidentate (N, S) as well as neutral mono-dentate (S) complexes. Anti-bacterial activity studies were carried out for these complexes as well as the ligands against Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli; Klebsiella pneumoniae) in which all the complexes (except complexes 2 and 6) as well as the ligands (except L3) showed anti-bacterial activity. In addition to the biological studies, colorimetric sensing study using silver nanoparticles was also carried out where, ligands L1 and L3 showed agglomeration effects.

α-glucosidase is an essential enzyme located at the brush border of intestines. It is an important therapeutic target for type II diabetes. Herein we have designed a library of novel α-arylketones as inhibitors of α-glucosidase (yeast origin) via scaffold hopping and bioisosteric modification of known inhibitors of α-glucosidase. The design was validated through molecular docking that revealed strong binding interactions of the newly designed compounds against α-glucosidase. A library comprising of 15 compounds was synthesized in a combinatorial fashion, where the advanced amide intermediates were accessed through “shot gun” synthesis. The final compounds were characterized by 1H, 13C-NMR and with high resolution mass spectroscopy. In vitro screening of the compounds against yeast α-glucosidase revealed substantial inhibition with IC50s in the range of 4–10 μM (the standard drug acarbose inhibits α-glucosidase with an IC50 of 9.95 μM). Reaction kinetics suggested mixed type inhibition. Finally, in vivo studies of the most active compound 3c against Streptozotocin induced male albino Wistar rats revealed that its administration in the rats for about 4 weeks lead to a highly significant (P 3c had better control over FBG in contrast to high-dose.

A new library of pyrido-pyrrolidine hybrid compounds were designed, developed and screened for their antidiabetic property with α-glucosidase. The design is based on preliminary screening of key fragments identified from literature reported α-glucosidase inhibitors and antidiabetic compounds. The most active fragments were stitched to provide a pyrido-pyrrolidine hybrid molecule as a new motif. A library of these compounds were synthesized and screened against a series of α-glycosidases. Subsequently, compound 3k was the most efficacious analog with IC50 of 0.56 μM. Photoluminescence study and circular dichroism experiments indicated that compound 3k modulates the primary and secondary structure of the enzyme. It successfully brings down the fasting blood glucose level for streptozotocin (STZ, 70 mg/kg, Intraperitoneal) induced type I diabetic male Sprague-Dawley rats (250–320 g). At lower concentration, compound 3k slightly stimulates proliferation of BRIN-BD11 (α-glucose responsive beta cells from rat pancreas islets that secretes insulin) cells.

Context: Albizia odoratissima (L. f.) Benth has been used in Indian folk medicine to treat numerous inflammatory pathologies, such as leprosy, ulcers, burns and asthma. Objective: To evaluate the antioxidant and antimicrobial properties of A. odoratissima. Materials and methods: Dried leaves of A. odoratissima were extracted in organic solvents (hexane, chloroform, ethyl acetate, and methanol). The total phenolic content (TPC) and total flavonoid content (TFC) were determined using the Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. The antioxidant activity was examined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide (H2O2), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS), and ferric reducing antioxidant power (FRAP) assays. The antibacterial activity was examined using minimum inhibitory concentration (MIC) and the minimum bacterial concentration (MBC), determined by broth microdilution method against Gram-negative bacteria (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Proteus vulgaris) and Gram-positive bacterium (Staphylococcus aureus). Results: The TPC ranged from 4.40 ± 1.06 to 1166.66 ± 31.85 mg GAE/g of dry weight (DW), and the TFC ranged from 48.35 ± 3.62 to 109.74 ± 1.84 mg QE/g of DW. The IC50 values of the ethyl acetate extract for DPPH, ABTS, and H2O2 were 10.96 ± 0.40, 4.35 ± 0.07, and 163.82 ± 1.52 μg/mL, respectively. Both methanol and ethyl acetate extracts demonstrated effective antibacterial activity with MICs and MBCs values ranging 136–546 μg/mL and 273–1093 μg/mL, respectively, against the tested pathogenic species. Conclusions: The leaves of A. odoratissima showed potent free radical scavenging property and antimicrobial activity.

Herein we have reported design, synthesis and in vitro biological evaluation of a library of bicyclic lactams that led to the discovery of compounds 6 and 7 as a novel class of α-glucosidase inhibitors. They inhibited α-glucosidase (yeast origin) in a mixed type of inhibition with an IC50 of ∼150 nM. Molecular docking studies further substantiated screening results. Interestingly phenotypic screening of this library against the human malaria parasite revealed 7 as a potent antiplasmodial agent.

The global preponderance of diabetes mellitus has prompted the medical community to opt for various therapeutic solutions to curb this menace. One of the means involved controlling the post prandial hyperglycemia. α-Glucosidase inhibitors are known to be excellent agents for controlling postprandial hyperglycemia. Different classes of α-glucosidase inhibitors have been discovered. In this context, a diverse library of substituted furopyridinediones (12a–v) was designed as potential inhibitors of α-glucosidase, using an intuitive scaffold hopping approach (which was further rationalized by molecular docking). They were synthesized in one step via an aldol condensation reaction of the furopyridinedione scaffold and appropriate aldehydes. The compounds were screened against α-glucosidase using acarbose as the reference inhibitor. Among the screened compounds, 12p transpired to be the lead candidate with an IC50 of 0.24 μM. Lineweaver–Burke analysis of 12p indicated that it is a mixed inhibitor. X-ray crystallography of 12p further confirmed its structure. Molecular modelling studies and molecular dynamic simulation experiments were performed against a homology model of α-glucosidase to observe the binding interaction of 12p with the enzymes.

Herein, we report a diversity-oriented-synthesis (DOS) approach for the synthesis of biologically relevant molecular scaffolds. Our methodology enables the facile synthesis of fused N-heterocycles, spirooxoindolones, tetrahydroquinolines, and fused N-heterocycles. The two-step sequence starts with a chiral-bicyclic-lactam-directed enolate-addition/substitution step. This step is followed by a ring-closure onto the built-in scaffold electrophile, thereby leading to stereoselective carbocycle- and spirocycle-formation. We used in silico tools to calibrate our compounds with respect to chemical diversity and selected drug-like properties. We evaluated the biological significance of our scaffolds by screening them in two cancer cell-lines. In summary, our DOS methodology affords new, diverse scaffolds, thereby resulting in compounds that may have significance in medicinal chemistry.

In the present study, we have demonstrated the diversity oriented synthesis of nitrogen heterocycles viz. chiral piperidinones, quinolizidinones and diaryl pyrrolidinones from Michael adducts generated via a TiCl4-catalyzed highly stereoselective Michael reaction with nitrostyrenes and an Evans chiral auxiliary. We also reported a Cu-4,4’-(isopropyl)-substituted isopropylidene-bridged 2,2’-bis-1,3’-oxazoline catalyst mediated catalytic asymmetric version of this reaction. In silico analysis is utilized to evaluate the diversity of the set of compounds against shape space (PMI), polar surface area (PSA) calculations and relevant drug like properties (viz. HBA, HBD, PSA, mol. wt., log P and log D). Finally, the molecules were screened against microorganisms to assess their antimicrobial properties.