SYNTHESIS OF FUSED PYRIMIDINES DERIVATIVES AND MANNICH BASES AND ASSESS OF THEIR ANTIBACTERIAL ACTIVITY, LASER EFFICACY AND MOLECULAR DOCKING

Fused pyrimidines gain an increasing interest as being a precursor for biologically active new compounds. The fused pyrimidine derivatives (1-5) were prepared by condensation of the 1,8-diamine naphthalene with some medical compounds in the presence of ammonium chloride as a dehydration agent for the water molecule and toluene as a solvent. Mannich base compounds (6-10) were prepared by reacting pyrimidines (1-5) with formaldehyde and 4-methoxyaniline. A microwave method was used in preparing the compounds. The prepared compounds were characterized by physical methods, through melting points and color, as well as by spectroscopic methods such as FT-IR and 1H-NMR. The purity of the prepared compounds was evaluated using TLC. The bioactivity of these compounds was tested against two types of bacteria, i.e. Escherichia coli and Staphylococcus aureus. The results of bioactivity showed an antibacterial activity compared to the standard drugs Cephalexin and Amoxicillin. The stability of selected compounds was evaluated by laser irradiation for (10, 20, 30, 40) seconds, and was found to be stable and did not decompose with a 30 seconds exposure. On the other hand, their color was changed at 40 seconds of exposure. Molecular docking studies were conducted to examine how some of the synthesized compounds bind to the putative target, SARS COV2 RNA-dependent RNA polymerase. The study concluded that some of the prepared compounds showed promising antibacterial and antiviral bioactivities. Further in vitro and in vivo toxicological and pharmacological studies are required to evaluate the possibility of using these compounds as a medicine.

Corrigendum: Synthesis and Cytotoxic Activity of Novel Indole Derivatives and Their in silico Screening on Spike Glycoprotein of SARS-CoV-2.

[This corrects the article DOI: 10.3389/fmolb.2021.637989.].

Advanced MoS2 nanocomposite materials for the synthesis of valuable pharmaceuticals

Rampant industrialization has played pivotal role in generation of polluting materials threatening ecology, environment and biosphere reserves. Amongst various pollutants, nitroarmatics are key components of non-biodegradable organic dyes, insecticides having toxic and carcinogenic effect on human health. Furthermore, aromatic hydrocarbons are widespread contaminants of ground water. Therefore, these waste materials are generally degraded by advanced oxidation process to carbon dioxide and water. But, these organic waste materials instead of complete mineralization can be valorized to valuable pharmaceuticals. For example, nitroaromatics can be valorized to tertiary amine or N-Mannich bases. N-Mannich bases are important pharmacophores and used as anti-microbial, anti-viral, anti-HIV, anti-inflammatory, analgesics and RSK2 inhibitory. Ethylbenzene is an important industrial waste can be used as building block for the synthesis of α-ketoamides. These α-ketoamides are significant pharmacophores can be used as the broad-spectrum antibiotics for COVID-19. Presently, COVID-19 is a global pandemic affecting billions of people. To deliver doses to such a big population would be a challenge. Therefore, we can use the industrial waste materials for the synthesis of valuable pharmacophors to boost the economy. To effectively catalyze the transformation of these industrial wastes into valuable products, cost-effective, readily available catalytic materials will be investigated. Earth abundant transition metals like Cu, Co, Zn, Ni, Zr etc. supported over 2D transition metal dichalcogenides can be used as the desirable candidates for the synthesis of pharmacophors from industrial waste. These catalytic materials will be prepared by hydrothermal or reverse micelle microemusion technique form metal salts or metal dithiocarbamates based single source molecular precursors.

Synthesis and Cytotoxic Activity of Novel Indole Derivatives and Their in silico Screening on Spike Glycoprotein of SARS-CoV-2.

This work investigated the interaction of indole with SARS-CoV-2. Indole is widely used as a medical material owing to its astounding biological activities. Indole and its derivatives belong to a significant category of heterocyclic compounds that have been used as a crucial component for several syntheses of medicine. A straightforward one-pot three-component synthesis of indole, coupled with Mannich base derivatives 1a-1j, was synthesized without a catalyst. The products were confirmed by IR, 1H-NMR, 13C-NMR, mass spectra, and elemental analysis. The indole derivatives were tested for cytotoxic activity, using three cancer cell lines and normal cell lines of Human embryonic kidney cell (HEK293), liver cell (LO2), and lung cell (MRC5) by MTT assay using doxorubicin as the standard drug. The result of cytotoxicity indole compound 1c (HepG2, LC50-0.9 µm, MCF-7, LC50-0.55 µm, HeLa, LC50-0.50 µm) was found to have high activity compared with other compounds used for the same purpose. The synthesized derivatives have revealed their safety by exhibiting significantly less cytotoxicity against the normal cell line (HEK-293), (LO2), and (MRC5) with IC50 > 100 µg/ml. Besides, we report an in silico study with spike glycoprotein (SARS-CoV-2-S). The selective molecules of compound 1c exhibited the highest docking score -2.808 (kcal/mol) compared to other compounds. This research work was successful in synthesizing a few compounds with potential as anticancer agents. Furthermore, we have tried to emphasize the anticipated role of indole scaffolds in designing and discovering the much-awaited anti-SARS CoV-2 therapy by exploring the research articles depicting indole moieties as targeting SARS CoV-2 coronavirus.