Correlation between Molecular Docking and the Stabilizing Interaction of HOMO-LUMO: Spirostans in CHK1 and CHK2, an In Silico Cancer Approach.

Checkpoint kinases 1 and 2 (CHK1 and CHK2) are enzymes that are involved in the control of DNA damage. At the present time, these enzymes are some of the most important targets in the fight against cancer since their inhibition produces cytotoxic effects in carcinogenic cells. This paper proposes the use of spirostans (Sp), natural compounds, as possible inhibitors of the enzymes CHK1 and CHK2 from an in silico analysis of a database of 155 molecules (S5).

Syntheses and medicinal chemistry of spiro heterocyclic steroids.

There is compelling evidence that incorporating a heterocyclic moiety into a steroid can alter its pharmacological and pharmacokinetic properties, driving intense interest in the synthesis of such hybrids among research groups. In this review, we present an overview of recent synthetic methodologies, spanning the period from 2000 to 2023, for the preparation of spiro heterocyclic steroids. The compounds surveyed encompass four-, five-, six-, and seven-membered heterocycles appended to various positions of steroidal backbones, with spirocycles containing oxygen, nitrogen, and sulfur atoms being predominant.

: Antioxidant Activity and In Silico Central Nervous System Potential.

(GB) extracts have been used in clinical studies as an alternative therapy for Alzheimer's disease (AD), but the exact bioaction mechanism has not yet been elucidated. In this work, an in silico study on GB metabolites was carried out using SwissTargetPrediction to determine the proteins associated with AD. The resulting proteins, AChE, MAO-A, MAO-B, β-secretase and γ-secretase, were studied by molecular docking, resulting in the finding that kaempferol, quercetin, and luteolin have multitarget potential against AD.

Essential Oil: Extraction, GC-MS, Phytochemical Analysis, Antioxidant Activity, and In Silico Molecular Docking for Protein Targets Related to CNS.

This study analyzed the chemical composition of essential oil from Puebla, México, assessed its antioxidant activity, and evaluated in silico protein-compound interactions related to central nervous system (CNS) physiology. GC-MS analysis identified myrcene (8.76%), Z-geranial (27.

Comparative Analysis of Antimicrobial Antibodies between Mild and Severe COVID-19.

Patients with 2019 coronavirus disease (COVID-19) exhibit a broad spectrum of clinical presentations. A person's antimicrobial antibody profile, as partially shaped by past infection or vaccination, can reflect the immune system health that is critical to control and resolve the infection. We performed an explorative immunoproteomics study using microbial protein arrays displaying 318 full-length antigens from 77 viruses and 3 bacteria.

Epoxide of diosgenin acetate synthesis: DoE for diastereoselective yield optimization, antimicroibial, antioxidant and antiproliferative effects.

Diosgenin and its derivatives have proved a huge importance in diverse biological activities. The optimized production of the diastereoisomers of the epoxide of diosgenin acetate by means of mCPBA is reported herein. This transformation had a previous design of experiments using the application of a statistical factorial DoE of 4 parameters (n), where one variable is varied at a time, while others stay constant.

22-Oxocholestanes SPGP4 and SPGP8: in Silico and in Vitro Study as Activators of Plant Growth Promotion.

The 22-oxocholestanes compounds have shown an outstanding plant growth promoting activity; they have similar bioactivity as brassinosteroids, so they are normally named as brassinosteroid analogs thinking that they also impact on the known receptor BRI1. However, in silico studies allow us to predict interactions with other receptors and thus it's possible to evaluate them, through receptors of gibberellins, auxins, jasmonates, strigolactones and the protein associated with the BRI1 gene. This article describes the bioactivity of structures SPGP4 and SPGP8 as plant growth-promoting compounds.

Fused Pyrroles in Cholestane and Norcholestane Side Chains: Acaricidal and Plant Growth-Promoting Effects.

Herein, we describe the synthesis and characterization of fused pyrroles in cholestane and norcholestane side chains derived from kryptogenin and diosgenin, respectively. Both conventional and microwave heating techniques were used to synthesize the steroidal pyrroles from primary amines, with the microwave method producing the highest yields. In particular, the norcholestane pyrroles were tested as acaricides against the two-spotted spider mite ( Koch) under laboratory conditions and as plant growth promoters on habanero pepper ( Jacq) under greenhouse conditions.

Microwave-enhanced synthesis of 26-amino-22-oxocholestanes and their cytotoxic activity.

The synthesis of a series of 26-amino-22-oxocholestanes derived from diosgenin was accomplished via the substitution of an iodine atom at C-26 by primary and secondary amines. The reactions were conducted in refluxing acetonitrile and through microwave-assisted heating. The latter shows significant improvements in terms of reaction times going from hours to a few minutes or even seconds for completion.

Stereoselective synthesis of (26R)-26-hydroxydiosgenin and its effect on the regulation of rat ovarian function.

The stereoselective cyclization of a C-16 acetylated 22,26-dioxocholestene derivative to give the spirostane E and F rings, under alkaline conditions, yields exclusively the (26R)-26-hydroxydiosgenin. Both experimental and computational data support the formation of a single diastereoisomer. The effect of diosgenin and (26R)-26-hydroxydiosgenin on rat ovary is also investigated.

-Hydroboration-oxidation products in Δ-steroids a hydroboration--hydroboration mechanism.

Herein, we report for the first time a "-hydroboration-oxidation product" isolated and characterized under traditional hydroboration-oxidation conditions using cholesterol and diosgenin as substrates. These substrates are excellent starting materials because of the rigidity and different structural environments around the double bond. Further investigations based on experimental evidence, in conjunction with theoretical studies, indicate that the formation of this -species occurs a -hydroboration of the major product to generate the corresponding Δ-structure and the subsequent hydroboration by the β-face.

Synthesis and biological in vitro evaluation of the effect of hydroxyimino steroidal derivatives on breast cancer cells.

Breast cancer is the most common cause of cancer death in women, according to Global Cancer Observatory. This fact forces scientists to continue in the search for effective treatments against this aggressive type of cancer. Breast cancer frequently metastasizes to other organs, most often the bones, lungs, and liver.

Mesoscale Assembly of Bisteroidal Esters from Terephthalic Acid.

A new series of bisteroidal esters was synthesized using a spacer group, sterols and sapogenins as substrates. Steroidal dimers were prepared in high yields employing diesters of terephthalic acid as linkages at the 3β, 3'β steroidal positions. In all attempts to crystallize bisteroids, it was observed that the compounds tended to self-organize in solution, which was detected when employing various solvent systems.

Apoptotic, necrotic, and antiproliferative activity of diosgenin and diosgenin glycosides on cervical cancer cells.

(25R)-spirost-5-en-3β-ol, also known as diosgenin (DSG), exerts antiproliferative activity on diverse cell lines, induces apoptosis, and acts as a chemopreventative agent. However, the relationship between DSG glycosides and apoptotic, necrotic, and antiproliferative activity remains unclear. It is in this regard that we report the antiproliferative, necrotic, and apoptotic activities of DSG and its glycoside derivatives: (25R)-spirost-5-en-3β-yl O-β-D-glucopyranoside (3GD), (25R)-spirost-5-en-3β-yl O-α-L-rhamnopyranosyl-(1 → 4)-β-D-glucopyranoside (3GRD); and (25R)-spirost-5-en-3β-yl O-α-L-rhamnopyranosyl-(1 → 2)-O-[α-L-rhamnopyranosyl-(1 → 4)]-β-D-glucopyranoside), also known as dioscin (DSC), in in vitro assays of cervical HeLa and CaSki cancer cells.

22-Oxocholestane oximes as potential anti-inflammatory drug candidates.

22-Oxocholestanes bearing the oxime functionality in the side chain have been synthesized from diosgenin and evaluated in vivo as anti-inflammatory agents in an acute inflammation mouse ear model, against the commercial glucocorticoid dexamethasone. The final compounds were all regioselectively obtained with an E configuration at the oxime double bond. The title compounds reduced ear-induced inflammation and edema.

Mimicking natural phytohormones. 26-Hydroxycholestan-22-one derivatives as plant growth promoters.

26-Hydroxycholestan-22-one derivatives with oxygenated functions in the rings A and/or B were successfully synthesized from diosgenin. After the modifications of rings A and B, the spiroketal side chain was selectively opened through a Lewis acid mediated acetolysis to afford the cholestane derivatives. These compounds incorporate pharmacophores, which mimic the activity of natural phytohormones and show high growth promoting activity in Mexican rice cultivars using the rice lamina inclination test.

Antiproliferative, Cytotoxic, and Apoptotic Activity of Steroidal Oximes in Cervicouterine Cell Lines.

Steroidal sapogenins have shown antiproliferative effects against several tumor cell lines; and their effects on human cancer cells are currently under study. Changes in the functionality on the steroidal structure make it possible to modify the biological activity of compounds. Herein, we report the synthesis and in vitro antitumor activity of two steroidal oxime compounds on cervical cancer cells.

Effectiveness of etravirine-based therapy for treatment-experienced HIV-infected patients.

Introduction: Treatment options are limited for HIV-1-infected individuals who have received extensive previous antiretroviral therapy. ETV has shown significant clinical benefits in treatment-experienced HIV-1+ patients with antiretroviral resistance. The aim of this study was to evaluate the effectiveness of ETV plus optimized background regimen in real-life conditions in a cohort of highly HIV-1 antiretroviral-experienced patients.

Regioselective Spirostan E-Ring Opening for the Synthesis of Dihydropyran Steroidal Frameworks.

The regioselective opening of the ring E in spirostan sapogenins provides new dihydropyran derivatives. This novel side chain is obtained after a Lewis acid mediated acetolysis followed by an alkaline workup. The reaction mechanism is analyzed via density functional theory computations, and both experimental and computational data support the formation of an oxacarbenium intermediate.

Apoptotic and autophagic cell death induced by glucolaxogenin in cervical cancer cells.

The antiproliferative and cytotoxic activity of glucolaxogenin and its ability to induce apoptosis and autophagy in cervical cancer cells are reported. We ascertained that glucolaxogenin exerts an inhibitory effect on the proliferation of HeLa, CaSki and ViBo cells in a dose-dependent manner. Analysis of DNA distribution in the cell-cycle phase of tumor cells treated with glucolaxogenin suggests that the anti-proliferative activity of this steroid is not always dependent on the cell cycle.

Effectiveness and risk factors for virological outcome of darunavir-based therapy for treatment-experienced HIV-infected patients.

Objective: We evaluated the effectiveness of darunavir (DRV) treatment plus an optimized background regimen in 120 HIV-1 treatment-experienced patients.

Design: Retrospective cohort, multicenter study.

Methods: Adults >16 years with virological treatment failure starting therapy with a DRV-containing regimen were included.

Anal intraepithelial neoplasia among HIV-positive men who have sex with men.

Neoplasia is the second most common cause of mortality in HIV patients. The prevalence of anal cancer among men who have sex with men (MSM) has continued to increase since the introduction of antiretroviral therapy. We screened 94 HIV-infected MSM patients.

Risk factors associated with mortality in patients infected with influenza A/H1N1 in Mexico.

Background: Influenza virus pandemics vary dramatically in their severity and mortality. Thus, it is very important to identify populations with high risks of developing severe illness to reduce mortality in future pandemics. The purpose was to determine the mortality-associated risk factors in hospitalized Mexican patients infected with influenza A/H1N1.

22-Oxocholestanes as plant growth promoters.

The spirostanic steroidal side-chain of diosgenin and hecogenin was modified to produce 22-oxocholestane derivatives. This type of side-chain was obtained in good yields through a straightforward four-step pathway. These compounds show potent brassinosteroid-like growth promoting activity evaluated via the rice lamina joint inclination bioassay.