Thiazol-4(5H)-one analogs as potent tyrosinase inhibitors: Synthesis, tyrosinase inhibition, antimelanogenic effect, antioxidant activity, and in silico docking simulation
Bioorg Med Chem. 2023 Dec 24;98:117578. doi: 10.1016/j.bmc.2023.117578. Online ahead of print.ABSTRACTAs the β-phenyl-α,β-unsaturated carbonyl (PUSC) structure was previously identified to play a key role in tyrosinase inhibition, 14 analogs with a PUSC structure built on a thiazol-4(5H)-one scaffold were synthesized using Knoevenagel condensation to serve as potential tyrosinase inhibitors. Through mushroom tyrosinase inhibition experiments, two analogs 9 and 11 were identified as potent tyrosinase inhibitors, with 11 exhibiting an IC50 value of 0.4 ± 0.01 μM, which indicates its 26-fold greater potency than kojic ac...
Source: Bioorganic and Medicinal Chemistry - December 28, 2023 Category: Chemistry Authors: Yu Jung Park Hee Jin Jung Hye Jin Kim Hye Soo Park Jieun Lee Dahye Yoon Min Kyung Kang Ga Young Kim Sultan Ullah Dongwan Kang Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon Source Type: research
Synthesis and evaluation of druglike parameters via in silico techniques for a series of heterocyclic monosquarate-amide derivatives as potential carboxylic acid bioisosteres
Bioorg Med Chem. 2023 Dec 20;98:117565. doi: 10.1016/j.bmc.2023.117565. Online ahead of print.ABSTRACTHerein, we present a synthetic compound library comprising of 13 structurally diverse heterocyclic monosquarate-amide derivatives. The compounds featured in this library were designed as potential bioisosteric replacements carboxylic acid moiety's. A good selection of the compounds presented exhibit unique molecular architecture and have shown promising results following in silico evaluation of 'druglike properties' using Swiss ADME. The research presented in this work focuses on the preparation of derivatives of 3,4-dihyd...
Source: Bioorganic and Medicinal Chemistry - December 24, 2023 Category: Chemistry Authors: N Long A Le Gresley A Wozniak S Brough S P Wren Source Type: research
ω-(5-Phenyl-2H-tetrazol-2-yl)alkyl-substituted glycine amides and related compounds as inhibitors of the amine oxidase vascular adhesion protein-1 (VAP-1)
Bioorg Med Chem. 2023 Dec 12;98:117558. doi: 10.1016/j.bmc.2023.117558. Online ahead of print.ABSTRACTVascular adhesion protein-1 (VAP-1), also known as plasma amine oxidase or semicarbazide-sensitive amine oxidase, is an enzyme that degrades primary amines to aldehydes with the formation of hydrogen peroxide and ammonia. Among others, it plays a role in inflammatory processes as it can mediate the migration of leukocytes from the blood to the inflamed tissue. We prepared a series of ω-(5-phenyl-2H-tetrazol-2-yl)alkyl-substituted glycine amides and related compounds and tested them for inhibition of purified bovine plasma...
Source: Bioorganic and Medicinal Chemistry - December 24, 2023 Category: Chemistry Authors: Timo P östges Florian Galster Jan Kampschulze Walburga Hanekamp Matthias Lehr Source Type: research
Synthesis and evaluation of druglike parameters via in silico techniques for a series of heterocyclic monosquarate-amide derivatives as potential carboxylic acid bioisosteres
Bioorg Med Chem. 2023 Dec 20;98:117565. doi: 10.1016/j.bmc.2023.117565. Online ahead of print.ABSTRACTHerein, we present a synthetic compound library comprising of 13 structurally diverse heterocyclic monosquarate-amide derivatives. The compounds featured in this library were designed as potential bioisosteric replacements carboxylic acid moiety's. A good selection of the compounds presented exhibit unique molecular architecture and have shown promising results following in silico evaluation of 'druglike properties' using Swiss ADME. The research presented in this work focuses on the preparation of derivatives of 3,4-dihyd...
Source: Bioorganic and Medicinal Chemistry - December 24, 2023 Category: Chemistry Authors: N Long A Le Gresley A Wozniak S Brough S P Wren Source Type: research
ω-(5-Phenyl-2H-tetrazol-2-yl)alkyl-substituted glycine amides and related compounds as inhibitors of the amine oxidase vascular adhesion protein-1 (VAP-1)
Bioorg Med Chem. 2023 Dec 12;98:117558. doi: 10.1016/j.bmc.2023.117558. Online ahead of print.ABSTRACTVascular adhesion protein-1 (VAP-1), also known as plasma amine oxidase or semicarbazide-sensitive amine oxidase, is an enzyme that degrades primary amines to aldehydes with the formation of hydrogen peroxide and ammonia. Among others, it plays a role in inflammatory processes as it can mediate the migration of leukocytes from the blood to the inflamed tissue. We prepared a series of ω-(5-phenyl-2H-tetrazol-2-yl)alkyl-substituted glycine amides and related compounds and tested them for inhibition of purified bovine plasma...
Source: Bioorganic and Medicinal Chemistry - December 24, 2023 Category: Chemistry Authors: Timo P östges Florian Galster Jan Kampschulze Walburga Hanekamp Matthias Lehr Source Type: research
Synthesis and evaluation of druglike parameters via in silico techniques for a series of heterocyclic monosquarate-amide derivatives as potential carboxylic acid bioisosteres
Bioorg Med Chem. 2023 Dec 20;98:117565. doi: 10.1016/j.bmc.2023.117565. Online ahead of print.ABSTRACTHerein, we present a synthetic compound library comprising of 13 structurally diverse heterocyclic monosquarate-amide derivatives. The compounds featured in this library were designed as potential bioisosteric replacements carboxylic acid moiety's. A good selection of the compounds presented exhibit unique molecular architecture and have shown promising results following in silico evaluation of 'druglike properties' using Swiss ADME. The research presented in this work focuses on the preparation of derivatives of 3,4-dihyd...
Source: Bioorganic and Medicinal Chemistry - December 24, 2023 Category: Chemistry Authors: N Long A Le Gresley A Wozniak S Brough S P Wren Source Type: research
ω-(5-Phenyl-2H-tetrazol-2-yl)alkyl-substituted glycine amides and related compounds as inhibitors of the amine oxidase vascular adhesion protein-1 (VAP-1)
Bioorg Med Chem. 2023 Dec 12;98:117558. doi: 10.1016/j.bmc.2023.117558. Online ahead of print.ABSTRACTVascular adhesion protein-1 (VAP-1), also known as plasma amine oxidase or semicarbazide-sensitive amine oxidase, is an enzyme that degrades primary amines to aldehydes with the formation of hydrogen peroxide and ammonia. Among others, it plays a role in inflammatory processes as it can mediate the migration of leukocytes from the blood to the inflamed tissue. We prepared a series of ω-(5-phenyl-2H-tetrazol-2-yl)alkyl-substituted glycine amides and related compounds and tested them for inhibition of purified bovine plasma...
Source: Bioorganic and Medicinal Chemistry - December 24, 2023 Category: Chemistry Authors: Timo P östges Florian Galster Jan Kampschulze Walburga Hanekamp Matthias Lehr Source Type: research
Synthesis and evaluation of druglike parameters via in silico techniques for a series of heterocyclic monosquarate-amide derivatives as potential carboxylic acid bioisosteres
Bioorg Med Chem. 2023 Dec 20;98:117565. doi: 10.1016/j.bmc.2023.117565. Online ahead of print.ABSTRACTHerein, we present a synthetic compound library comprising of 13 structurally diverse heterocyclic monosquarate-amide derivatives. The compounds featured in this library were designed as potential bioisosteric replacements carboxylic acid moiety's. A good selection of the compounds presented exhibit unique molecular architecture and have shown promising results following in silico evaluation of 'druglike properties' using Swiss ADME. The research presented in this work focuses on the preparation of derivatives of 3,4-dihyd...
Source: Bioorganic and Medicinal Chemistry - December 24, 2023 Category: Chemistry Authors: N Long A Le Gresley A Wozniak S Brough S P Wren Source Type: research
ω-(5-Phenyl-2H-tetrazol-2-yl)alkyl-substituted glycine amides and related compounds as inhibitors of the amine oxidase vascular adhesion protein-1 (VAP-1)
Bioorg Med Chem. 2023 Dec 12;98:117558. doi: 10.1016/j.bmc.2023.117558. Online ahead of print.ABSTRACTVascular adhesion protein-1 (VAP-1), also known as plasma amine oxidase or semicarbazide-sensitive amine oxidase, is an enzyme that degrades primary amines to aldehydes with the formation of hydrogen peroxide and ammonia. Among others, it plays a role in inflammatory processes as it can mediate the migration of leukocytes from the blood to the inflamed tissue. We prepared a series of ω-(5-phenyl-2H-tetrazol-2-yl)alkyl-substituted glycine amides and related compounds and tested them for inhibition of purified bovine plasma...
Source: Bioorganic and Medicinal Chemistry - December 24, 2023 Category: Chemistry Authors: Timo P östges Florian Galster Jan Kampschulze Walburga Hanekamp Matthias Lehr Source Type: research
Structure activity relationship and target prediction for ABX464 analogues in Caenorhabditis elegans
Bioorg Med Chem. 2023 Dec 3;98:117540. doi: 10.1016/j.bmc.2023.117540. Online ahead of print.ABSTRACTGlobal challenges with treatment failures and/or widespread resistance in parasitic worms against commercially available anthelmintics lend impetus to the development of new anthelmintics with novel mechanism(s) of action. The free-living nematode Caenorhabditis elegans is an important model organism used for drug discovery, including the screening and structure-activity investigation of new compounds, and target deconvolution. Previously, we conducted a whole-organism phenotypic screen of the 'Pandemic Response Box' (from ...
Source: Bioorganic and Medicinal Chemistry - December 22, 2023 Category: Chemistry Authors: Harrison T Shanley Aya C Taki Nghi Nguyen Tao Wang Joseph J Byrne Ching-Seng Ang Michael G Leeming Shuai Nie Nicholas Williamson Yuanting Zheng Neil D Young Pasi K Korhonen Andreas Hofmann Tim N C Wells Abdul Jabbar Brad E Sleebs Robin B Gasser Source Type: research
Structure activity relationship and target prediction for ABX464 analogues in Caenorhabditis elegans
Bioorg Med Chem. 2023 Dec 3;98:117540. doi: 10.1016/j.bmc.2023.117540. Online ahead of print.ABSTRACTGlobal challenges with treatment failures and/or widespread resistance in parasitic worms against commercially available anthelmintics lend impetus to the development of new anthelmintics with novel mechanism(s) of action. The free-living nematode Caenorhabditis elegans is an important model organism used for drug discovery, including the screening and structure-activity investigation of new compounds, and target deconvolution. Previously, we conducted a whole-organism phenotypic screen of the 'Pandemic Response Box' (from ...
Source: Bioorganic and Medicinal Chemistry - December 22, 2023 Category: Chemistry Authors: Harrison T Shanley Aya C Taki Nghi Nguyen Tao Wang Joseph J Byrne Ching-Seng Ang Michael G Leeming Shuai Nie Nicholas Williamson Yuanting Zheng Neil D Young Pasi K Korhonen Andreas Hofmann Tim N C Wells Abdul Jabbar Brad E Sleebs Robin B Gasser Source Type: research
Elongation of N < sup > 6 < /sup > -benzyladenosine scaffold via Pd-catalyzed C-C bond formation leads to derivatives with antiflaviviral activity
Bioorg Med Chem. 2023 Dec 10;98:117552. doi: 10.1016/j.bmc.2023.117552. Online ahead of print.ABSTRACTDecoration of nucleoside analogues with lipophilic groups often leads to compounds with improved antiviral activity. For example, N6-benzyladenosine derivatives containing elongated lipophilic substituents in the benzyl core efficiently inhibit reproduction of tick-borne encephalitis virus (TBEV), while N6-benzyladenosine itself potently inhibits reproduction of human enterovirus A71 (EV-A71). We have extended a series of N6-benzyladenosine analogues using effective synthetic methods of CC bond formation based on Pd-cataly...
Source: Bioorganic and Medicinal Chemistry - December 21, 2023 Category: Chemistry Authors: Anastasia A Zenchenko Mikhail S Drenichev Evgeny V Khvatov Victoria I Uvarova Alexander S Goryashchenko Vasilisa S Frolenko Evgenia V Karpova Liubov I Kozlovskaya Dmitry I Osolodkin Aydar A Ishmukhametov Sergey N Mikhailov Vladimir E Oslovsky Source Type: research
Sialyl Lewis < sup > X < /sup > glycomimetics bearing an extended anionic chain targeting E- and P- selectin binding sites
Bioorg Med Chem. 2023 Dec 9;98:117553. doi: 10.1016/j.bmc.2023.117553. Online ahead of print.ABSTRACTNeutrophil binding to vascular P- and E-selectin is the rate-limiting step in the recruitment of immune cells to sites of inflammation. Many diseases, including sickle cell anemia, post-myocardial infarction reperfusion injury, and acute respiratory distress syndrome are characterized by dysregulated inflammation. We have recently reported sialyl Lewisx analogues as potent antagonists of P- and E-selectin and demonstrated their in vivo immunosuppressive activity. A key component of these molecules is a tartrate diester that...
Source: Bioorganic and Medicinal Chemistry - December 21, 2023 Category: Chemistry Authors: Audrey Belouin Ryan D Simard Mathieu Joyal Wael Maharsy Alice Lau Michel Pr évost Mona Nemer Yvan Guindon Source Type: research
Elongation of N < sup > 6 < /sup > -benzyladenosine scaffold via Pd-catalyzed C-C bond formation leads to derivatives with antiflaviviral activity
Bioorg Med Chem. 2023 Dec 10;98:117552. doi: 10.1016/j.bmc.2023.117552. Online ahead of print.ABSTRACTDecoration of nucleoside analogues with lipophilic groups often leads to compounds with improved antiviral activity. For example, N6-benzyladenosine derivatives containing elongated lipophilic substituents in the benzyl core efficiently inhibit reproduction of tick-borne encephalitis virus (TBEV), while N6-benzyladenosine itself potently inhibits reproduction of human enterovirus A71 (EV-A71). We have extended a series of N6-benzyladenosine analogues using effective synthetic methods of CC bond formation based on Pd-cataly...
Source: Bioorganic and Medicinal Chemistry - December 21, 2023 Category: Chemistry Authors: Anastasia A Zenchenko Mikhail S Drenichev Evgeny V Khvatov Victoria I Uvarova Alexander S Goryashchenko Vasilisa S Frolenko Evgenia V Karpova Liubov I Kozlovskaya Dmitry I Osolodkin Aydar A Ishmukhametov Sergey N Mikhailov Vladimir E Oslovsky Source Type: research
Sialyl Lewis < sup > X < /sup > glycomimetics bearing an extended anionic chain targeting E- and P- selectin binding sites
Bioorg Med Chem. 2023 Dec 9;98:117553. doi: 10.1016/j.bmc.2023.117553. Online ahead of print.ABSTRACTNeutrophil binding to vascular P- and E-selectin is the rate-limiting step in the recruitment of immune cells to sites of inflammation. Many diseases, including sickle cell anemia, post-myocardial infarction reperfusion injury, and acute respiratory distress syndrome are characterized by dysregulated inflammation. We have recently reported sialyl Lewisx analogues as potent antagonists of P- and E-selectin and demonstrated their in vivo immunosuppressive activity. A key component of these molecules is a tartrate diester that...
Source: Bioorganic and Medicinal Chemistry - December 21, 2023 Category: Chemistry Authors: Audrey Belouin Ryan D Simard Mathieu Joyal Wael Maharsy Alice Lau Michel Pr évost Mona Nemer Yvan Guindon Source Type: research
