Melphalan: Recent insights on synthetic, analytical and medicinal aspects
Eur J Med Chem. 2022 May 27;238:114494. doi: 10.1016/j.ejmech.2022.114494. Online ahead of print.ABSTRACTCancer is an uncontrolled expansion of atypical cells in the body. These unusual cells are labelled as cancerous or malignant cells. Melphalan, an anticancer drug which is imperatively recognized under the class of alkylating agents. It exhibits broad spectrum antitumor activity, as observed in ovarian cancer, breast cancer, etc. However, it is mainly utilized in the management of multiple myeloma. Several studies across the globe suggest that resistance to melphalan is the major concern that leads to relapsed myeloma. ...
Source: European Journal of Medicinal Chemistry - June 6, 2022 Category: Chemistry Authors: Rakesh Pahwa Jatin Chhabra Raj Kumar Rakesh Narang Source Type: research

Novel quinoline-based derivatives: A new class of PDE4B inhibitors for adjuvant-induced arthritis
Eur J Med Chem. 2022 May 28;238:114497. doi: 10.1016/j.ejmech.2022.114497. Online ahead of print.ABSTRACTA total of 31 quinoline-based derivatives were designed and synthesized to develop novel anti-inflammatory drugs. After the toxicity of synthetic compounds to RAW264.7 cells were evaluated in vitro, their anti-inflammatory activity was assessed by inhibiting lipopolysaccharide (LPS)-induced NO production levels in the RAW264.7 cells. Among the derivatives, compound f4 had the best anti-inflammatory activity, which could reduce the production of pro-inflammatory cytokines NO, IL-1β, and TNF-α with corresponding IC50 va...
Source: European Journal of Medicinal Chemistry - June 6, 2022 Category: Chemistry Authors: Siqi Xing Weizheng Fan Junhua Chen Jiyu Du Tongtong Liu Shuanghong Dong Jucheng Xia Peipei Liu Dexing Zou Li Cai Zeng Li Source Type: research

Therapeutic potentials and structure-activity relationship of 1,3-benzodioxole N-carbamothioyl carboxamide derivatives as selective and potent antagonists of P2X4 and P2X7 receptors
Eur J Med Chem. 2022 May 27;238:114491. doi: 10.1016/j.ejmech.2022.114491. Online ahead of print.ABSTRACTP2X receptors (P2XRs) are ligand-gated membrane ion channels. ATP binds to open these ion channels and results in membrane depolarization. Hyperactivities and overexpression of P2XRs are related to various pathophysiological conditions such as chronic pain, inflammatory diseases, rheumatoid arthritis, various neurological disorders, and cancer. Inhibition of P2XRs is a potential drug target that is an emerging therapeutic tool for disease management. In the present study, 17 new compounds were synthesized based on 1,3-b...
Source: European Journal of Medicinal Chemistry - June 6, 2022 Category: Chemistry Authors: Abid Mahmood Alexander Villinger Jamshed Iqbal Source Type: research

Bacterial type I signal peptidase inhibitors - Optimized hits from nature
Eur J Med Chem. 2022 May 26;238:114490. doi: 10.1016/j.ejmech.2022.114490. Online ahead of print.ABSTRACTThe ever-increasing number of bacteria resistant to the currently available antibacterial agents is a great medical problem today, and new antibiotics with novel mechanisms of action are urgently needed. Among the validated antibacterial drug targets against which new classes of antibiotics might be directed is bacterial type I signal peptidase (SPase I), an essential part of the Tat and Sec secretory systems. SPase I is responsible for the hydrolysis of the N-terminal signal peptides from proteins secreted across the c...
Source: European Journal of Medicinal Chemistry - June 6, 2022 Category: Chemistry Authors: Natalia Sza łaj Andrea Benediktsdottir Dominika Rusin Anders Karl én Sherry L Mowbray Anna Wi ęckowska Source Type: research

Design and synthesis of highly TRAIL expression HDAC inhibitors based on ONC201 to promote apoptosis of colorectal cancer
Eur J Med Chem. 2022 May 27;238:114484. doi: 10.1016/j.ejmech.2022.114484. Online ahead of print.ABSTRACTActivation of the TRAIL proapoptotic pathway can promote cancer cell apoptosis. Histone deacetylases (HDACs) also are promising drug targets for cancers, and their synergistic effect with TRAIL can improve the inhibitory effect on cancer cells. Therefore, the development of highly TRAIL-sensitive HDAC inhibitors might be a promising strategy for the treatment of cancers. We synthesized a series of HDAC inhibitors by introducing effective fragments sensitive to TRAIL. Compound IIc showed good inhibitory activity against ...
Source: European Journal of Medicinal Chemistry - June 1, 2022 Category: Chemistry Authors: Hao Cui Zan Hu Kang Yang Jingkun Huang Yichao Wu Quanwei Chen Ran Wei Penfeng Wang Hui Wang Hongmei Li Yadong Chen Tao Lu Yuqin Yao Yong Zhu Source Type: research