Modeling studies on the role of vitamins B1 (thiamin), B3 (nicotinamide), B6 (pyridoxamine), and caffeine as potential leads for the drug design against COVID-19.

In response to the COVID-19 pandemic, and the lack of effective and safe antivirals against it, we adopted a new approach in which food supplements with vital antiviral characteristics, low toxicity, and fast excretion have been targeted. The structures and chemical properties of the food supplements were compared to the promising antivirals against SARS-COV-2. Our goal was to exploit the food supplements to mimic the topical antivirals' functions but circumventing their severe side effects, which has limited the necessary dosage needed to exhibit the desired antiviral activity. On this line, after a comparative structural analysis of the chemicals mentioned above, and investigation of their potential mechanisms of action, we selected caffeine and some compounds of the vitamin B family and further applied molecular modeling techniques to evaluate their interactions with the RDB domain of the Spike protein of SARS-CoV-2 (SC2Spike) and its corresponding binding site on human ACE-2 (HssACE2). Our results pointed to vitamins B1 and B6 in the neutral form as potential binders to the HssACE2 RDB binding pocket that might be able to impair the SARS-CoV-2 mechanism of cell invasion, qualifying as potential leads for experimental investigation against COVID-19.

Design, structure-activity relationship study and biological evaluation of the thieno[3,2-c]isoquinoline scaffold as a potential anti-cancer agent.

Several derivatives of a series that share a thienoisoquinoline scaffold have demonstrated potent activity against cancer cell lines A549, HeLa, HCT-116, and MDA-MB-231 in the submicromolar concentration range. Structure-activity relationship (SAR) studies on a range of derivatives aided in identifying key pharmacophores in the lead compound. A series of compounds have been identified as the most promising with submicromolar IC50 values against a lung cancer cell line (A549). Microscopy studies of cancer cells treated with the lead compound revealed that it causes mitotic arrest and disrupts microtubules. Further evaluation via an in vitro microtubule polymerization assay and competition studies indicate that the lead compound binds to tubulin via the colchicine site.

Virtual screening, docking, and dynamics of potential new inhibitors of dihydrofolate reductase from Yersinia pestis.

In the present work, we propose to design drugs that target the enzyme dihydrofolate redutase (DHFR) as a means of a novel drug therapy against plague. Potential inhibitors of DHFR from Yersinia pestis (YpDHFR) were selected by virtual screening and subjected to docking, molecular dynamics (MD) simulations, and Poisson-Boltzmann surface area method, in order to evaluate their interactions in the active sites of YpDHFR and human DHFR (HssDHFR). The results suggested selectivity for three compounds that were further used to propose the structures of six new potential selective inhibitors for YpDHFR.

Domino Michael-O-alkylation: one-pot synthesis of dialkyl 4-oxo-2,3-dihydro-2,3-furandicarboxylates.

The KSCN-catalyzed reaction of dialkyl acetylenedicarboxylates with pentane-2,4-dione in acetone, led to dialkyl 2-(1-acetyl-2-oxopropyl)-2-butenedioates in excellent yields. When these reactions were carried out in MEK (butane-2-one), dialkyl 4-oxo-2,3-dihydro-2,3-furandicarboxylates were obtained exclusively. This difference in reactivity is discussed in terms of the possibility of cationic exchange in butane-2-one.

One-pot synthesis of functionalized 4-oxo-2-thioxo-1,3-thiazinanes from primary amines, CS(2), and itaconic anhydride.

An efficient synthesis of 2-(3-alkyl-4-oxo-2- thioxo-1,3-thiazinan-5-yl)acetic acids is described via a three-component reaction between primary amines, CS(2), and itaconic anhydride.

Three-component synthesis of functionalized 5-oxo-4,5-dihydroindeno[1,2-b]pyrans.

Protonation of the reactive intermediates produced in the reaction between alkyl(aryl) isocyanides and dialkyl acetylenedicarboxylates by indan-1,3-dione leads to vinylnitrilium cations, which undergo carbon centered Michael type addition with the conjugate base of the CH-acid to produce functionalized 5-oxo-4,5-dihydroindeno[1,2-b]pyrans.