Design and Synthesis of Different Aryl Substituted 1,3,4-Oxadiazole-imidazo[1,5-a]pyridine Derivatives as Anticancer Agents

A new series of 1,3,4-oxadiazole incorporated imidazo[1,5-a]pyridine derivatives was prepared. Anticancer activity of all the obtained compounds was investigated by employing MTT assay. Among them, six compounds showed most prominent anticancer activity than etoposide

BIOANALYTICAL METHOD DEVELOPMENT AND VALIDATION OF MARALIXIBAT IN RAT PLASMA BY LC-MS/MS DETECTION AND ITS APPLICATION TO A PHARMACOKINETIC STUDY

Objective: To quantify Maralixibat in rat plasma utilizing liquid-liquid extraction (LLE) approach, a practical, efficient, and accurate LC-MS/MS approach was devised. Methods: As an internal standard (IS), Elobixibat was adopted. Utilizing an Agilent eclipse C18, 150mm x 4.6mm, 3.5µm column, the drug separation was accomplished using an isocratic mobile phase entailing acetonitrile (ACN) and buffer (1ml Tri fluoro acetic acid into 1liter water and stir well. Filtered through 0.22µ membrane filter paper) composition of 70:30 (v/v), dispensed at 1.0 mL/min. Results: Multiple reaction monitoring (MRM) positive mode allowed for the simultaneous detection of Maralixibat and Elobixibat exhibiting proton adducts around m/z 676.0278-290.3625 and m/z 696.8541-480.6328, correspondingly. The correlation coefficient (r2) of the approach was ≥0.99977 across a linearity concentration spanning between 5.00 –100.00 ng/mL. This technique achieved intra-day accuracy and precision between 99.31-100.93% and 0.22 -6.55%, correspondingly. Across 3 freeze-thaw sessions, bench top testings, and postoperative stability investigations, Maralixibat was shown to be stable. Conclusion: Through intravenous injection, this approach was effectively utilized in rats for studying the drug's pharmacokinetics

Synthesis of molnupiravir (MK-4482, EIDD-2801): a promising oral drug for the treatment of COVID-19 starting from cytidine

The present work describes the synthesis of molnupiravir by employing commercially available inexpensive materials in two steps with an overall yield of 85.7%. The synthetic methodology starts with an eco-friendly starting material, that is, cytidine and establishes an alternative way to avoid costly enzyme mediated reactions. This synthetic strategy involves a selective acylation of cytidine as the first key step followed by the second step, that is, hydroxamination reaction. The major advantage of this protocol is that it is completely free of protection and deprotection reactions. Chemoselective acylation of cytidine’s primary alcohol was achieved using isobutyryl chloride, Et3N, and DMF solvent (89.3% yield). The aqueous phase transformation was achieved for the hydroxamination reaction with a 96% yield.</p

Total phenolic content and antioxidant activity of morinda tinctoria leaves

The antioxidant activity and total phenolic content of Morinda tinctoria leaves was evaluated. The successively extracted leaves of Morinda tinctoria using various solvents was analyzed for their total phenolic content. The extracts were subjected to column chromatography for the isolation of bioactive molecules. In vitro antioxidant activity was evaluated by employing different assays, including 2,2-diphenyl-1-picrylhydrazyl, nitric oxide scavenging assay and phosphomolybdenum reducing power assay. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging efficacy of hexane extract is significant at higher concentration (500 μg/ml- 91.2±0.05%) and the efficacy at lower concentration is more significant for ethyl acetate extract (100 μg/ml - 65.1±0.05%). The total phenolic content was highest in methanol extract (5.30±0.011 μg/mg). Cynarin, a hydroxy cinnamic acid was isolated from chloroform extract; oleuropein, a polyphenolic iridoid was isolated from methanol extract. The results obtained suggeted that Morinda tinctoria leaf extracts possessed antioxidant properties and might offer protection from free radicals. Two compounds, cynarin and oleuropein were reported for the first time from Morinda tinctoria leaves

Ultrasound Assisted Cu-catalyzed Ullmann-Goldberg Type Coupling-cyclization in a Single Pot: Synthesis and inSsilico Evaluation of 11H-pyrido[2,1-b]quinazolin-11-ones Against SARS-CoV-2 RdRp

The in silico evaluation of 11H-pyrido[2,1-b]quinazolin-11-one derivatives against SARS-CoV-2 RdRp was undertaken based on the reports on antiviral activities of this class of compounds in addition to the promising interactions of the antiviral drug penciclovir as well as quinazoline derivatives with SARS-CoV-2 RdRp in silico. The target compounds were prepared via an Ullmann–Goldberg type coupling followed by the subsequent cyclization (involving amidation) in a single pot. The methodology involved a CuI-catalyzed reaction of 2-iodobenzoate ester with 2-aminopyridine or quinolin-2-amine or thiazol-2-amine under ultrasound to give the expected products in acceptable (51–93%) yields. The molecular interactions of the synthesized 11H-pyrido[2,1-b]quinazolin-11-one derivatives with the SARS-CoV-2 RdRp (PDB: 7AAP) were evaluated in silico. The study suggested that though none of these compounds showed interactions better than penciclovir but the compound 3a and 3n appeared to be comparable along with 3b seemed to be nearly comparable to favipiravir and remdesivir. The compound 3n with the best binding energy (-79.85 Kcal/mol) participated in the H-bond interactions through its OMe group with THR556 as well as ARG624 and via the N-5 atom with the residue SER682. The in silico studies further suggested that majority of the compounds interacted with the main cavity of active site pocket whereas 3h and 3o that showed relatively lower binding energies (-66.06 and -66.28 Kcal/mol) interacted with the shallow cavity underneath the active site of SARS CoV-2 RdRp. The study also revealed that a OMe group was favourable for interaction with respect to its position in the order C-8 \u3e C-1 \u3e C-2. Further, the presence of a fused quinoline ring was tolerated whereas a fused thiazole ring decreased the interaction significantly. The in silico predictions of pharmacokinetic properties of 3a, 3b and 3n indicated that besides the BBB (Blood Brain Barrier) penetration potential these molecules may show a good overall ADME. Overall, the regioisomers 3a, 3b and 3n have emerged as molecules of possible interest in the context of targeting COVID-19

Factors associated with adverse COVID-19 outcomes in patients with psoriasis : insights from a global registry–based study

Background: The multimorbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse outcomes of coronavirus disease 2019 (COVID-19), but the data are limited. Objective: Our aim was to characterize the course of COVID-19 in patients with psoriasis and identify factors associated with hospitalization. Methods: Clinicians reported patients with psoriasis with confirmed/suspected COVID-19 via an international registry, Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection. Multiple logistic regression was used to assess the association between clinical and/or demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviors. Results: Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% were receiving a nonbiologic, and 10% were not receiving any systemic treatment for psoriasis. In all, 348 patients (93%) were fully recovered from COVID-19, 77 (21%) were hospitalized, and 9 (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted odds ratio [OR] = 1.59 per 10 years; 95% CI = 1.19-2.13), male sex (OR = 2.51; 95% CI = 1.23-5.12), nonwhite ethnicity (OR = 3.15; 95% CI = 1.24-8.03), and comorbid chronic lung disease (OR = 3.87; 95% CI = 1.52-9.83). Hospitalization was more frequent in patients using nonbiologic systemic therapy than in those using biologics (OR = 2.84; 95% CI = 1.31-6.18). No significant differences were found between classes of biologics. Independent patient-reported data (n = 1626 across 48 countries) suggested lower levels of social isolation in individuals receiving nonbiologic systemic therapy than in those receiving biologics (OR = 0.68; 95% CI = 0.50-0.94). Conclusion: In this international case series of patients with moderate-to-severe psoriasis, biologic use was associated with lower risk of COVID-19-related hospitalization than with use of nonbiologic systemic therapies; however, further investigation is warranted on account of potential selection bias and unmeasured confounding. Established risk factors (being older, being male, being of nonwhite ethnicity, and having comorbidities) were associated with higher hospitalization rates