Structurally modified compounds of hydroxychloroquine, remdesivir and tetrahydrocannabinol against main protease of SARS-CoV-2, a possible hope for COVID-19: Docking and molecular dynamics simulation studies.

Now a days, more than 200 countries faces the health crisis due to epidemiological disease COVID-19 caused by SARS-CoV-2 virus. It will cause a very high impact on world's economy and global health sector. Earlier the structure of main protease (Mpro) protein was deposited in the RCSB protein repository. Hydroxychloroquine (HCQ) and remdesivir were found to effective in treatment of COVID-19 patients. Here we have performed docking and molecule dynamic (MD) simulation study of HCQ and remdesivir with Mpro protein which gave promising results to inhibit Mpro protein in SARS-CoV-2. On the basis of results obtained we designed structurally modified 18 novel derivatives of HCQ, remdesivir and tetrahydrocannabinol (THC) and carried out docking studies of all the derivatives. From the docking studies six molecules DK4, DK7, DK10, DK16, DK17 and DK19 gave promising results and can be use as inhibitor for Mpro of SARS-CoV-2 to control COVID-19 very effectively. Further, molecular dynamics simulation of one derivative of HCQ and one derivative of tetrahydrocannabinol showing excellent docking score was performed along with the respective parent molecules. The two derivatives gave excellent docking score and higher stability than the parent molecule as validated with molecular dynamics (MD) simulation for the binding affinities towards Mpro of SARS-CoV-2 thus represented as strong inhibitors at very low concentration.

Aldehydes: magnificent acyl equivalents for direct acylation.

From the viewpoint of meeting the current green chemistry challenges in chemical synthesis, there is a need to disseminate how the cocktail of acylation and activation can play a pivotal role in affording bioactive acylated products comprising substituted ketone motifs in fewer reaction steps, with higher atom-economy and improved selectivity. In recent years, a significant number of articles employing the title compounds "aldehydes" as magnificent acylation surrogates which are less toxic and widely applicable have been published. This review sheds light on the compounds use for selective acylation of arene, heteroarene and alkyl (sp3, sp2 and sp) C-H bonds by proficient utilization of the C-H activation strategy. Critical insights into selective acylation of diverse moieties for the synthesis of bioactive compounds are presented in this review that will enable academic and industrial researchers to understand the mechanistic aspects involved and fruitfully employ these strategies in designing novel molecules.

Antigiardial activity of novel triazolyl-quinolone-based chalcone derivatives: when oxygen makes the difference.

Giardiasis is a common diarrheal disease worldwide caused by the protozoan parasite Giardia intestinalis. It is urgent to develop novel drugs to treat giardiasis, due to increasing clinical resistance to the gold standard drug metronidazole (MTZ). New potential antiparasitic compounds are usually tested for their killing efficacy against G. intestinalis under anaerobic conditions, in which MTZ is maximally effective. On the other hand, though commonly regarded as an 'anaerobic pathogen,' G. intestinalis is exposed to relatively high O2 levels in vivo, living attached to the mucosa of the proximal small intestine. It is thus important to test the effect of O2 when searching for novel potential antigiardial agents, as outlined in a previous study [Bahadur et al. (2014) Antimicrob. Agents Chemother. 58, 543]. Here, 45 novel chalcone derivatives with triazolyl-quinolone scaffold were synthesized, purified, and characterized by high resolution mass spectrometry, (1)H and (13)C nuclear magnetic resonance and infrared spectroscopy. Efficacy of the compounds against G. intestinalis trophozoites was tested under both anaerobic and microaerobic conditions, and selectivity was assessed in a counter-screen on human epithelial colorectal adenocarcinoma cells. MTZ was used as a positive control in the assays. All the tested compounds proved to be more effective against the parasite in the presence of O2, with the exception of MTZ that was less effective. Under anaerobiosis eighteen compounds were found to be as effective as MTZ or more (up to three to fourfold); the same compounds proved to be up to >100-fold more effective than MTZ under microaerobic conditions. Four of them represent potential candidates for the design of novel antigiardial drugs, being highly selective against Giardia trophozoites. This study further underlines the importance of taking O2 into account when testing novel potential antigiardial compounds.

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles.

A microwave-assisted synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles from a phenylazide, propargyloxybenzaldehyde and a 1,2-diaminobenzene is proposed.

O(2)-dependent efficacy of novel piperidine- and piperazine-based chalcones against the human parasite Giardia intestinalis.

Giardia intestinalis is the most frequent protozoan agent of intestinal diseases worldwide. Though commonly regarded as an anaerobic pathogen, it preferentially colonizes the fairly oxygen-rich mucosa of the proximal small intestine. Therefore, when testing new potential antigiardial drugs, O2 should be taken into account, since it also reduces the efficacy of metronidazole, the gold standard drug against giardiasis. In this study, 46 novel chalcones were synthesized by microwave-assisted Claisen-Schmidt condensation, purified, characterized by high-resolution mass spectrometry, (1)H and (13)C nuclear magnetic resonance, and infrared spectroscopy, and tested for their toxicity against G. intestinalis under standard anaerobic conditions. As a novel approach, compounds showing antigiardial activity under anaerobiosis were also assayed under microaerobic conditions, and their selectivity against parasitic cells was assessed in a counterscreen on human epithelial colorectal adenocarcinoma cells. Among the tested compounds, three [30(a), 31(e), and 33] were more effective in the presence of O2 than under anaerobic conditions and killed the parasite 2 to 4 times more efficiently than metronidazole under anaerobiosis. Two of them [30(a) and 31(e)] proved to be selective against parasitic cells, thus representing potential candidates for the design of novel antigiardial drugs. This study highlights the importance of testing new potential antigiardial agents not only under anaerobic conditions but also at low, more physiological O2 concentrations.

Assessment of the Efficacy of L-Lysine Sulfate vis-à-vis L-Lysine Hydrochloride as Sources of Supplemental Lysine in Broiler Chickens.

In this study the effects of L-lysine hydrochloride (containing 78.8% available lysine as crystalline lysine) and L-lysine sulfate (containing 51% available lysine in bacterial cell mass) as source of supplemental lysine in broiler chickens was assessed. The basal diet was supplemented with either L-lysine hydrochloride or L-lysine sulfate to meet lysine requirement. Lysine supplementation irrespective of source improved (P < .05) live weight and food conversion. Live weight and food conversion ratio of the L-lysine sulfate group was superior (P < .05) to the L-lysine hydrochloride group. Supplementation of lysine to the basal diet improved breast meat yield (P < .05). Meat protein content and protein accretion increased (P < .01) when L-lysine sulfate was supplemented. Nutrient metabolizability, N retention, protein utilization efficiency and live weight gain : lysine intake ratio also improved (P < .01) with L-lysine sulfate. A fasting trial conducted after the completion of the feeding trial indicated that the birds receiving L-lysine sulfate retained more of their live weight than the control and the L-lysine hydrochloride dietary groups (P < .05). It was concluded that due to the retained bacterial cell mass, L-lysine sulfate may be a superior source of supplemental lysine than L-lysine hydrochloride for broiler chickens.