Letters in Organic Chemistry - Volume 20, Issue 4, 2023

The presence of N-heterocyclic ring systems as promising features in the molecular skeleton of FDA-approved drugs, underlie the remarkable contributions of these heterocyclic nuclei in the field of medicine. Despite instability risks associated with the COVID pandemic, the US FDA approved 50 drugs (36 NMEs and 14 biological products) in the year 2021. The active ingredients of 32 drugs out of these 36 NMEs (almost 89%) contain saturated, partially unsaturated and aromatic Nheterocyclic moieties in their molecular assemblies, hence dominating the medicinal approvals. While 27 molecules (75% of these NMEs drugs) are prominent small NMEs. Herein, we have considered profiling those FDA-approved 27 small-molecule drugs which are decorated with N-heterocycles as privileged scaffolds. These drugs are grouped on the basis of a number of N-heterocycles present in their structural framework. The spectrum of these drugs in terms of their structural features and medicinal importance is summarized in this review. Also, the pertinent analyses of their drug-likeliness conferring some general pharmacokinetic principles are highlighted.

Breast cancer is one of the most frequent invasive malignancies in women globally and the leading cause of mortality. The HER2 target is an important therapeutic option for treating breast cancer. In the present study, efforts have been made to virtually screen the natural kinase inhibitors through molecular docking. A total of 800 HER2 protein inhibitor compounds were selected to screen out the potential inhibitors of the HER2 protein. The docking study demonstrated that these HER2 protein inhibitors confirm the strong binding interaction with HER2 protein based on the docking score, indicating that kinase inhibitors can play a major role in preventing breast cancer. Among all the inhibitors, the flavanone compound named 6-C-(3-Hydroxyisopentyl) eriodictyol, IUPAC: 2-(3, 4- dihydroxyphenyl)-5, 7-dihydroxy-6-(3-hydroxy-3-methylbutyl)- 2, 3-dihydrochromen-4-one observed to have the maximum docking score value of (-8.717), indicating the highest binding affinity with HER2 protein which might serve as the promising compound for the development of a new class of drug to combat breast cancer.

The pyrazolone subordinate, aminopyrine, has been broken down tentatively and hypothetically for its vibrational frequencies. The chemical shift values and symphonious vibrational frequencies as obtained at B3LYP/CAM-B3LYP/6-31G after employing proper scaling techniques appear to match acceptably with the test perceptions. The hypothetical spectrograms for NMR, FT-IR and UV spectra of aminopyrine have been likewise developed and contrasted with the trial spectra. Determined hyperpolarizability (4.531 ×10^-30 esu) showed that the particle might have a nonlinear optical (NLO) component with non-zero qualities. An investigation of hydrogen bonding, utilizing mathematical and topological boundaries, has additionally been conducted.

A series of fused 3-[{(1-aminomethyl)-5,7-dimethyl-2-oxoindolin-3-ylidene}amino]-2- phenylquinazolin-4(3H)-ones 4(i-ix) has been designed and synthesized by the condensation reaction between 3-amino -2-phenylquinazolin-4(3H)-one and 5,7-dimethylindolin-2,3-dione, followed by aminomethylation with secondary amines in the presence of formaldehyde and were also screened for their antifungal potential against human pathogenic fungi. The structures of all synthesized compounds have been established with the help of elemental and spectral analysis, such as NMR, FT-IR and mass spectrometry. Out of all synthesized compounds 4(i-ix), theoretical calculation was performed for 3-((5,7-dimethyl-1-(morpholinomethyl)-2-oxoindolin-3-ylidene)amino)-2-phenylquinazolin- 4(3H)-one (4i). The experimental 1H was compared with theoretically calculated values by using B3LYP/6-31G (d, p) level through the GIAO approach. The higher value of first-order hyper polarizability predicted (4i) may be used as NLO material. To explore molecular stability, three intermolecular interactions, such as N8—O22··· H47, C37—H64 ···N12, and C23—H45 ···C30, were observed through the QTAIM approach. In addition, global reactivity descriptor and molecular electrostatic potential were computed for the prediction of reactivity and reactive sites.

A novel series of 2, 6-diaryl-3-(4-methylpiperazin-1-yl) piperidin-4-one (2a-2f) derivatives was synthesized. All the synthesized compounds were characterized by FT-IR, NMR, Mass spectrum, and CHN analysis. NMR spectral analyses were performed unambiguously by their one-dimensional (¹H NMR and ¹³C NMR) and two-dimensional (¹H-¹H COSY and ¹H-¹³C HSQC) NMR. From the NMR spectral data, the compounds (2a-2f) were found to have normal chair conformation with an equatorial orientation of all the phenyl groups at C-2 and C-6 and the piperazine ring at C-3. The target compounds 2a-2f were subjected to in silico docking and ADME prediction. From the result of in silico docking study, compound 2d showed a good docking score (-8.2 kcal/mol) compared to the standard drug ciprofloxacin (-7.8 kcal/mol). The synthesized piperidine-4-one compounds (2a-2f) demonstrated good to moderate activity against gram-positive and gram-negative strains. From the result of in silico ADME prediction, most of the compounds exhibited good drug scores and druglikeness properties.

Background: Cancer has become a significant universal health problem. Anticancer drugs control the chemicals that sacrifice cancer cells by inhibiting their growth in their cell cycle. Interestingly, as much as boron nitride nanosheets and boron nitride nanotubes are degradable and non-toxic, they can act as suitable drug carriers for antitumor drugs and deliver them into target cells. Objective: In the present study, the encapsulation of diethylstilbestrol as an anticancer drug into the boron nitride (8,8) nanotube was investigated for the first time using the density functional theory: M06-2X and the natural bond orbital methods in the gas phase. Methods: Using natural bond orbital analysis, the charge transfer between diethylstilbestrol drug and boron nitride nanotubes (8,8)/ diethylstilbestrol complex was explored. Results: Based on the results obtained from the calculation of encapsulation energy, it was found that the adsorption process was favorable. The interaction effects of diethylstilbestrol drug and boron nitride (8,8) nanotube on the natural bond orbital charge, the chemical shift parameters, and electronic properties were also evaluated. Conclusion: This study revealed that boron nitride (8,8) nanotubes can be a suitable carrier for diethylstilbestrol drug delivery. The ultra violet-visible spectra of diethylstilbestrol drug and the boron nitride (8,8) nanotubes/diethylstilbestrol complex were computed using time-dependent density functional theory (: M06-2X calculations.

This research paper presents a green, safe and easy synthesis of trans-chalcones under ultrasound irradiation in the presence of anionic resins. Several trans-Chalcones have been obtained following an environmentally friendly methodology using Amberlyte IRA-410 and Amberlyte IRA-400 resins as heterogeneous and efficient catalysts. The products of the condensation reaction were generally synthesized in good yields and the analysis confirmed their structures well.

The process of hydrogen bond donor accelerating the cycloaddition of epoxides with CO2 is green access to high economic value cyclocarbonate derivatives. However, hydrogen bond donor still has certain limitations such as poor biocompatibility and narrow substrate scope. Our group found that folic acid could promote the coupling reaction of epoxides and CO2 through hydrogen-bonding. The reaction was used to synthesize various cyclocarbonate derivatives in good to high yields with the aid of folic acid and TBAB. In addition, benzoic acids and 2,4-quinazoline dione were synthesized in the presence of CuCl2/folic acid and PdCl2/folic acid, respectively. The reaction mechanism was proposed based on previous reports and control experiments.

Increasing microbial resistance has become a threatening situation for humanity. Therefore, new active antimicrobial compounds are needed to be synthesized. Copper complexes, one of these types of biologically active compounds, appear as compounds with a wide range of biological uses. Many scientific investigations have shown that copper complexes have antibacterial, antimalarial, anti- inflammatory, and anticancer activities. In this study, a new bis-copper(II) complex based on a hydrazone ligand (Ligand A) was designed, synthesized, and evaluated as an antimicrobial agent. The characterization of copper(II) complex was mainly done with single crystal X-ray diffraction and other spectroscopic techniques (FT-IR and Elemental Analysis). In order to determine the chemical structure and vibrational properties, theoretical calculations were carried out. Vibrational wavenumbers and HOMO-LUMO energy gap of copper(II) complex were investigated using the DFT/ B3LYP method, LanL2DZ basis set. The agreement between experimental and theoretical results were observed. Information about local and global chemical activity, the electrophilic and nucleophilic nature of copper(II) complex were theoretically obtained. The ligand and its copper(II) complex were investigated for their antibacterial effects against Gram (+) and Gram (-) bacteria. The results show that copper(II) complex was more effective in reducing cell viability of Enterococcus faecalis, Staphylococcus aureus, and Staphylococcus epidermidis than free hydrazone ligand, whereas it was not effective towards Gram (-) forms. Copper(II) complex displayed the highest antimicrobial activity against Staphylococcus aureus ATCC 25923 and S. epidermidis CECT 4183. The results suggested that the designed metal complex can be a good alternative to similar complex systems as an antimicrobial agent. Besides, there are not many studies in the literature on the antibacterial activities of the copper( II) complex and its ligand. For this reason, the study will contribute to the literature.