Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions.

We report a synthetic methodology for the construction of the fused heterocyclic compounds pyrido[2,1-b]quinazolin-9(1H)-ones and pyrrolo[2,1-b]quinazolin-9(1H)-ones through an AgOTf-catalyzed intramolecular alkyne hydroamination reaction. The methodology is applicable to a wide scope of substrates and produces a series of fused quinazolinone heterocycles in good to excellent yields.

New Pyrazolo-Benzimidazole Mannich Bases with Antimicrobial and Antibiofilm Activities.

A new series of pyrazolo-benzimidazole hybrid Mannich bases were synthesized, characterized by 1H-NMR, 13C-NMR, IR, UV-Vis, MS, and elemental analysis. In vitro cytotoxicity of the new compounds studied on fibroblast cells showed that the newly synthesized pyrazolo-benzimidazole hybrid derivatives were noncytotoxic until the concentration of 1 µM and two compounds presented a high degree of biocompatibility. The antibacterial and antibiofilm activity of the newly synthesized compounds was assayed on Gram-positive Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Gram-negative Pseudomonas aeruginosa ATCC27853, Escherichia coli ATCC25922 strains. All synthesized compounds 5a-g are more active against all three tested bacterial strains Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Escherichia coli ATCC25922 than reference drugs (Metronidazole, Nitrofurantoin), with the exception of compounds 5d and 5g, which are less active compared to Nitrofurantoin, and all synthesized compounds 5a-g are more active against Pseudomonas aeruginosa ATCC27853 compared to reference drugs (Metronidazole, Nitrofurantoin). Compound 5f showed the best activity against Staphylococcus aureus ATCC 25923, with a MIC of 150 µg/mL and has also inhibited the biofilm formed by all the bacterial strains, having an MBIC of 310 µg/mL compared to the reference drugs (Metronidazole, Nitrofurantoin).

Data to understand the nature of non-covalent interactions in the thiophene clusters.

We have reported herein the data to understand the nature and number of non-covalent interactions that stabilize the structures of the thiophene clusters. In addition, we have also provided the optimized Cartesian coordinates of all the structures of the investigated thiophene clusters. Initially, the geometries have been generated using the ABCluster code which performs a global optimization to locate local and global minima structures of molecular clusters. The located geometries have been optimized at the MP2/aug-cc-pVDZ level of theory using Gaussian 16 suite of programs. To understand the nature of non-covalent interactions, we have performed a quantum theory of atoms in molecules (QTAIM) analysis on all the structures of the thiophene dimer. Furthermore, the QTAIM analysis has been performed also on the most stable structure of the thiophene trimer and tetramer. We have used the AIMAll program to perform the QTAIM analysis. The data reported in this paper contains the critical points, the bonds paths and their related properties, for each investigated structures. Besides, the data contains the optimized Cartesian coordinates of all the investigated structures of the thiophene clusters. This can be use for any further investigations involving thiophene clusters. For further information and analysis, the reader is referred to the original related research article (Malloum and Conradie, 2022).

Synthesis and Anti-Cancer Applications of Benzimidazole Derivatives - Recent Studies.

BACKGROUND: Cancer is a life-threatening disease. Anti-cancer drugs are the focus of research. The heterocyclic molecules like benzimidazole occupy a central position in searching for novel and effective anti-cancer drugs. The medicinal chemists designed and synthesized several benzimidazole derivatives and conjugates to evaluate them as potential anti-cancer agents. OBJECTIVE: The purpose of this compilation of literature is to cover the progress of benzimidazole-based anti-cancer agents, their synthesis, and their evaluation for cancer disease treatment. METHODS: The recent literatures have been collected from various search engines and peer-reviewed journals. RESULTS: The compounds like benzimidazole derivatives of dehydroabietic acid, piperidyl benzimidazole carboxamide, benzimidazole-quinazolinone hybrids, benzimidazole-thiazole conjugate, and benzimidazole pendant cyanopyrimidine derivatives have been discussed in detail. CONCLUSION: This review article will help the medicinal chemists to design and synthesize benzimidazole-based molecules and evaluate them as anti-cancer agents.

QTAIM analysis dataset for non-covalent interactions in furan clusters.

Furan clusters are very important to understand the dynamics and properties of the furan solvent. They can be used combined with quantum cluster equilibrium theory to theoretically determine the thermodynamics properties of the furan solvent. To understand the structures of the furan clusters, one needs to understand the non-covalent interactions that hold the furan molecules together. In this paper, we have provided the data necessary to understand the non-covalent interactions in furan clusters. Firstly, the structures of the furan clusters have been generated using classical molecular dynamics as implemented in the ABCluster code. Secondly, the generated structures have been fully optimized at the MP2/aug-cc-pVDZ level of theory. The optimized Cartesian coordinates of all the investigated structures are reported in this work to enable further investigations of the furan clusters. These Cartesian coordinates will save computational time for all further investigations involving the furan clusters. Thirdly, to understand the nature of the non-covalent interactions in furan clusters, we have performed a quantum theory of atoms in molecule (QTAIM) analysis using AIMAll program. Using QTAIM, we have provided the critical points, bond paths and their related properties for all the investigated structures. These data can be used to identify and classify the non-covalent interactions in furan clusters. The reader can refer to the original article for further information and discussion of the data provided herein Malloum and Conradie (2022) [1].

Contemporary advances of cyclic molecules proposed for inflammation.

This review stretches insight about the advancement (2011-2021) of synthesized non-heterocyclic, heterocyclic and natural occurring cyclic molecules for inflammation. While inflammation is very significant in the abolition of pathogens and other causes of soreness, a protracted inflammatory procedure takes to outcomes in chronic disease that might finally affect in organ failure or damage. Thus, restraining the provocative process by the use of anti-inflammatory agents is chief in controlling this damage. It also reveals other pursuit along with their anti-inflammatory activity. Molecular docking studies represent most suitable PDB (Protein Data Bank) ID for the synthesized heterocyclic molecules with their selective inhibitor. It discusses the findings presented in recent research papers and provides understanding to researchers intended for the growth of newer combinations/molecules having littler side things.

Integrating virtual screening and biochemical experimental approach to identify potential anti-cancer agents from drug databank.

Chemical libraries constitute a reservoir of pharmacophoric molecules to identify potent anti-cancer agents. Virtual screening of heterocyclic compound library in conjugation with the agonist-competition assay, toxicity-carcinogenicity analysis, and string-based structural searches enabled us to identify several drugs as potential anti-cancer agents targeting protein kinase C (PKC) as a target. Molecular modeling study indicates that Cinnarizine fits well within the PKC C2 domain and exhibits extensive interaction with the protein residues. Molecular dynamics simulation of PKC-Cinnarizine complex at different temperatures (300, 325, 350, 375, and 400[Formula: see text]K) confirms that Cinnarizine fits nicely into the C2 domain and forms a stable complex. The drug Cinnarizine was found to bind PKC with a dissociation constant Kd of [Formula: see text]M. The breast cancer cells stimulated with Cinnarizine causes translocation of PKC-[Formula: see text] to the plasma membrane as revealed by immunoblotting and immunofluorescence studies. Cinnarizine also dose dependently reduced the viability of MDAMB-231 and MCF-7 breast cancer cells with an IC[Formula: see text] of [Formula: see text] and [Formula: see text]g/mL, respectively. It is due to the disturbance of cell cycle of breast cancer cells with reduction of S-phase and accumulation of cells in G1-phase. It disturbs mitochondrial membrane potentials to release cytochrome C into the cytosol and activates caspase-3 to induce apoptosis in cancer cells. The cell death was due to induction of apoptosis involving mitochondrial pathway. Hence, the current study has assigned an additional role to Cinnarizine as an activator of PKC and potentials of the approach to identify new molecules for anti-cancer therapy. Thus, in silico screening along with biochemical experimentation is a robust approach to assign additional roles to the drugs present in the databank for anti-cancer therapy.