Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors

In this study, amino-oxy-diarylquinolines were designed using structure-guided molecular hybridization strategy and fusing of the pharmacophore templates of nevirapine (NVP), efavirenz (EFV), etravirine (ETV, TMC125) and rilpivirine (RPV, TMC278). The anti-HIV-1 reverse transcriptase (RT) activity was evaluated using standard ELISA method, and the cytotoxic activity was performed using MTT and XTT assays. The primary bioassay results indicated that 2-amino-4-oxy-diarylquinolines possess moderate inhibitory properties against HIV-1 RT. Molecular docking results showed that 2-amino-4-oxy-diarylquinolines 8(a-d) interacted with the Lys101 and His235 residue though hydrogen bonding and interacted with Tyr318 residue though π-π stacking in HIV-1 RT. Furthermore, 8a and 8d were the most potent anti-HIV agents among the designed and synthesized compounds, and their inhibition rates were 34.0% and 39.7% at 1 µM concentration. Interestingly, 8a was highly cytotoxicity against MOLT-3 (acute lymphoblastic leukemia), with an IC50 of 4.63±0.62 µg/mL, which was similar with that in EFV and TMC278 (IC50 7.76±0.37 and 1.57±0.20 µg/ml, respectively). Therefore, these analogs of the synthesized compounds can serve as excellent bases for the development of new anti-HIV-1 agents in the near future. [...] © Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals: Table of contents  |  ...
Source: Drug Research - Category: Drugs & Pharmacology Authors: Tags: Original Article Source Type: research

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Publication date: Available online 8 October 2020Source: Clinical Lymphoma Myeloma and LeukemiaAuthor(s): Kirill A. Lyapichev, Narittee Sukswai, Evgeniya Angelova, Marian J. Kersh, Sherry Pierce, Marina Konopleva, Nitin Jain, Elias J. Jabbour, Jeffrey L. Jorgensen, Sa A. Wang, L. Jeffrey Medeiros, Joseph D. Khoury, Sergej Konoplev
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Abstract Incidence trends in acute lymphoblastic leukemia (ALL) demonstrate disparities by race and ethnicity. We used data from the Surveillance, Epidemiology and End Results Registry to evaluate patterns in ALL incidence from 2000-2016, including the association between the percent of people born in a foreign country at the county level and ALL incidence. Among 23,829 individuals of all ages diagnosed with ALL, 8,297 (34.8%) were Latinos, 11,714 (49.2%) were non-Latino (NL) Whites, and 1,639 (6.9%) were NL Blacks. Latinos had the largest increase in the age-adjusted incidence rate (AAIR) in this period compared ...
Source: Am J Epidemiol - Category: Epidemiology Authors: Tags: Am J Epidemiol Source Type: research
A 69-year-old man with newly diagnosed B-precursor acute lymphoblastic leukemia (B-ALL) had impaired consciousness (Glasgow coma scale [GCS] E4V4M6) on day 24 of remission induction therapy. Serum beta-D-glucan (61.0  pg/μL) and Aspergillus galactomannan antigens in the serum and cerebrospinal fluid (CSF) (both ≥5.0) were elevated. Computed tomography showed a nodule in the left lung. Magnetic resonance imaging (MRI) revealed multiple brain lesions, and brain biopsy confirmed aspergillosis (Fig. 1) accordin g to the updated invasive fungal disease definition (Donnelly et al., 2019).
Source: International Journal of Infectious Diseases - Category: Infectious Diseases Authors: Tags: Medical Imagery Source Type: research
Authors: Balsat M, Cacheux V, Carre M, Tavernier-Tardy E, Thomas X Abstract INTRODUCTION: Despite the significant progress that has been made over the last years in the front-line treatment of Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL), relapses are frequent and their treatment remains a challenge, especially among patients with resistant BCR-ABL1 mutations. AREAS COVERED: This manuscript reviews available data for the treatment of adult patients with relapsed/refractory Ph-positive ALL, with a focus on the role of tyrosine kinase inhibitors (TKIs), monoclonal antibodies, and immun...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
An infectious trigger for childhood acute lymphoblastic leukemia is hypothesized and we assessed the association between the rate, type, and critical exposure period for infections and the development of acute lymphoblastic leukemia. We conducted a matched case-control study using administrative databases to evaluate the association between the rate of infections and childhood acute lymphoblastic leukemia diagnosed between the ages of 2–14 years from Ontario, Canada and we used a validated approach to measure infections. In 1600 cases of acute lymphoblastic leukemia, and 16 000 matched cancer-free controls aged 2&nda...
Source: European Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Hematological cancers Source Type: research
Donor cell (DC) leukemia is a rare cause of relapse after allogeneic hematopoietic cell transplantation and usually presents as acute myeloid leukemia. Uncommonly, other DC ‐derived hematologic malignancies can occur and usually have a poor prognosis. AbstractDonor cell leukemia is a very rare cause of relapse after allogeneic hematopoietic cell transplantation (alloHCT). Herein, we describe an unprecedented case of donor cell ‐derived chronic myelomonocytic leukemia (CMML) presenting seven years after a 51‐year‐old man received a matched‐related alloHCT from his 59‐year‐old brother for T‐cell acute lymphoblastic leukemia.
Source: Clinical Case Reports - Category: General Medicine Authors: Tags: CASE REPORT Source Type: research
Conclusion: SLCO1B1 rs4149056 may serve as a determinant of MTX treatment toxicity in children with JIA. PMID: 33025831 [PubMed - as supplied by publisher]
Source: Scandinavian Journal of Rheumatology - Category: Rheumatology Authors: Tags: Scand J Rheumatol Source Type: research
B acute lymphoblastic leukemia/lymphoma (B-ALL) is a hematologic malignancy derived from B-cell progenitors.1 Significant advances in therapy for B-ALL patients have taken place over the past decades. The outcome of pediatric B-ALL has improved dramatically with 10 year overall survival (OS) of>90%.2 Notwithstanding, B-ALL outcomes among adults remain inferior with 5-year OS rate between 30% and 50%.3 Therefore, novel therapeutic options are needed for adults with B-ALL.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Commentary Source Type: research
Relapsed Acute Lymphoblastic Leukemia (ALL): Mutational Landscape  (study page |release notes)
Source: dbGaP, the database of Genotypes and Phenotypes - Category: Genetics & Stem Cells Tags: StudyRelease Source Type: research
AbstractIn the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as a standard approach for Philadelphia chromosome –positive acute lymphoblastic leukemia (Ph+ ALL) achieving complete remission (CR). However, the role of autologous hematopoietic stem cell transplantation (auto-HSCT) in adult patients achieving complete molecular remission (CMR) is an alternative, less toxic treatment options, especially for the patients who lack suitable donors and are unfit for allo-HSCT. Thus, we conducted a systematic review and meta-analysis to compare the effi...
Source: Annals of Hematology - Category: Hematology Source Type: research
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