Synthesis, molecular docking of new amide thiazolidine derived from isoniazid and studying their biological activity against cancer cells.

BCL2, an antiapoptotic protein, is overexpressed in many cancers, making it a good cancer treatment target. In 30 years, few BCL2 targeting agents have shown clinical significance. This work designed new amide thiazolidine derived from isoniazid targeting BCL2 and tested them on cancer cell lines, for binding affinities, the novel candidates were docked to the BCL2 target receptor. IC50 of compound A8 46.67 ± 0.9 and 57.14 ± 0.88 µg/ml against PC3 and HEPG2 respectively with docking score -7.6 Kcal/mol with 6GL8 make it the best compound in this series. Melting point, FT-IR, elemental microanalysis (CHN), 1HNMR, and 13CNMR confirmed chemical structures.Communicated by Ramaswamy H. Sarma.

New tamoxifen analogs for breast cancer therapy: synthesis, aromatase inhibition and in silico studies.

A new class of tamoxifen analogues, using McMurry reaction conditions, is described. The scheme involved the conversion of ketoprofen (6) into amide derivatives 7 and 8, by coupling with N1,N1-substituted propan-1,3-diamine derivatives in the presence DIC and HOB. Treatment of 7 and 8 with various ketones under McMurry reaction conditions afforded the tamoxifen analogues 9-16. All the analogues were screened in vitro for their aromatase inhibitory and antiproliferative activity against MCF-7 breast cancer cells. Compounds 10, 11 and 12 showed a potent activity against MCF-7 cell lines breast cancer with IC50 values of 0.070, 0.042 and 0.077 µM of selectivity index (SI) 3.0, 2.5 and 2.6, respectively. Further, 12 exhibited potent activity against estrogen receptor (14.7 ± 2.4 nM), while compound 10 was the most active analogues against aromatase with IC50 of (0.070 nM). Furthermore, all new compounds were docked into human placental aromatase enzyme and estrogen receptor and showed very good correlations with experimental IC50. Therefore, we can consider these designed compounds as starting scaffold to design an efficient drug against estrogen receptor and aromatase.Communicated by Ramaswamy H. Sarma.

Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2.

SARS-CoV-2 is a new generation of coronavirus, which was first determined in Wuhan, China, in December 2019. So far, however, there no effective treatment has been found to stop this new generation of coronavirus but discovering of the crystal structure of SARS-CoV-2 main protease (SARS-CoV-2 Mpro) may facilitate searching for new therapies for SARS-COV-2. The aim was to assess the effectiveness of available FDA approved drugs which can construct a covalent bond with Cys145 inside binding site SARS-CoV-2 main protease by using covalent docking screening. We conducted the covdock module MMGBSA module in the Schrodinger suite 2020-1, to examine the covalent bonding utilizing. Besides, we submitted the top three drugs to molecular dynamics simulations via Gromacs 2018.1. The covalent docking showed that saquinavir, ritonavir, remdesivir, delavirdine, cefuroxime axetil, oseltamivir and prevacid have the highest binding energies MMGBSA of -72.17, -72.02, -65.19, -57.65, -54.25, -51.8, and -51.14 kcal/mol, respectively. The 50 ns molecular dynamics simulation was conducted for saquinavir, ritonavir and remdesivir to evaluate the stability of these drugs inside the binding pocket of SARS-CoV-2 main protease. The current study provides a powerful in silico results, means for rapid screening of drugs as anti-protease medications and recommend that the above-mentioned drugs can be used in the treatment of SARS-CoV-2 in combined or sole therapy.Communicated by Ramaswamy H. Sarma.

Flavonoids in the Treatment of Diabetes: Clinical Outcomes and Mechanism to Ameliorate Blood Glucose Levels.

BACKGROUND: For thousands of years, natural food products have been used as a medicine for treating diseases that affect the human body, including diabetes mellitus (DM). Lately, several investigations have been performed on the flavonoid derivatives of plant origin, and their biological activity has been extensively studied. METHODS: Given our need to know more mechanisms for treating DM, we performed a thorough research review on treating diabetes mellitus based on flavonoids, their therapeutic potential, and biological action. RESULTS: Flavonoids reduce complications in addition to their vital role as effective supplements for preventing diabetes mellitus by regulating glucose metabolism, lipid profile, liver enzyme activity, a protein kinase inhibitor, PPAR, and AMPK with NF-κB. CONCLUSION: The articles that we reviewed showed the positive role of flavonoids, which in a certain way reduce diabetes, but their side effects still need to be studied further.This review is focused on describing the different types of dietary flavonoids along with their mechanisms of reducing blood glucose and enhancing insulin sensitivity, as well as their side effects.

Coumarins as Potential Antioxidant Agents Complemented with Suggested Mechanisms and Approved by Molecular Modeling Studies.

Syntheses of coumarins, which are a structurally interesting antioxidant activity, was done in this article. The modification of 7-hydroxycoumarin by different reaction steps was done to yield target compounds. Molecular structures were characterized by different spectroscopical techniques (Fourier transformation infrared and nuclear magnetic resonance). Antioxidant activities were performed by using various in vitro spectrophometric assays against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and hydrogen peroxide (H2O2). All compounds exhibited high efficiency as antioxidants compared to ascorbic acid. The highest efficiency scavenging activity was found for compound 3 (91.0 ± 5.0), followed by compounds 2 and 4 (88.0 ± 2.00; and 87.0 ± 3.00). Ascorbic acid C was used as a standard drug with a percentage inhibition of 91.00 ± 1.5. The mechanism of the synthesized compounds as antioxidants was also studied. Hartree-Fock-based quantum chemical studies have been carried out with the basis set to 3-21G, in order to obtain information about the three-dimensional (3D) geometries, electronic structure, molecular modeling, and electronic levels, namely HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital), to understand the antioxidant activity for the synthesized compounds.