Antibacterial and antitubercular evaluation of dihydronaphthalenone‐indole hybrid analogs

Kumar, Praveen; J, Renjitha; T, Fathimath Salfeena C; Ashitha, Kizhakkan Thiruthi; Keri, Rangappa S.; Varughese, Sunil; Somappa, Sasidhar B.

doi:10.1111/cbdd.12990

Cited by 32 publications

(1 citation statement)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Semisynthetic modification of therapeutically proven lead natural products is one of the most successful approaches to optimizing their pharmacological properties and also to explore their vivid mode of action. − We have previously reported a series of novel labdane-appended scaffolds with very promising antiobesity and antihyperlipidemic properties. , These encouraging discoveries provided the insights for us to continue our focused efforts on medicinal chemistry, − in particular natural-product-based semisynthetic modifications for the development of therapeutically improved scaffolds. Therefore, in the present work, we have rationally designed and synthesized a series of 27 new phytochemical entities (NPCEs), by the strategic inclusion of aromatic or heteroaromatic fragments to the labdane template via a linker-based molecular hybridization (Figure ) and explored their potential toward multifaceted inflammatory targets.…”

Section: Introductionmentioning

confidence: 99%

Linker-Based Pharmacophoric Design and Semisynthesis of Labdane Conjugates Active against Multi-Faceted Inflammatory Targets

Mohan,

Krishnan,

Madhusoodanan

et al. 2024

J. Agric. Food Chem.

Self Cite

View full text Add to dashboard Cite

Prolonged inflammation leads to the genesis of various inflammatory diseases such as atherosclerosis, cancer, inflammatory bowel disease, Alzheimer's, etc. The uncontrolled inflammatory response is characterized by the excessive release of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1alpha (IL-1α), and inflammatory enzymes such as cyclooxygenase-2 (COX-2). Hence, the downregulation of these inflammatory mediators is an active therapy to control aberrant inflammation and tissue damage. To address this, herein, we present the rational design and synthesis of novel phytochemical entities (NPCEs) through strategic linker-based molecular hybridization of aromatic/ heteroaromatic fragments with the labdane dialdehyde, isolated from the medicinally and nutritionally significant rhizomes of the plant Curcuma amada. To validate the anti-inflammatory potential, we employed a comprehensive in vitro study assessing its inhibitory effect on the COX-2 enzyme and other inflammatory mediators, viz., NO, TNF-α, IL-6, and IL-1α, in bacterial lipopolysaccharide-stimulated macrophages, as well as in-silico molecular modeling studies targeting the inflammation regulator COX-2 enzyme. Among the synthesized novel compounds, 5f exhibited the highest anti-inflammatory potential by inhibiting the COX-2 enzyme (IC 50 = 17.67 ± 0.89 μM), with a 4-fold increased activity relative to the standard drug indomethacin (IC 50 = 67.16 ± 0.17 μM). 5f also significantly reduced the levels of LPS-induced NO, TNF-α, IL-6, and IL-1α, much better than the positive control. Molecular mechanistic studies revealed that 5f suppressed the expression of COX-2 and pro-inflammatory cytokine release dose-dependently, which was associated with the inhibition of the NF-κB signaling pathway. This infers that the labdane derivative 5f is a promising lead candidate as an anti-inflammatory agent to further explore its therapeutic landscape.

show abstract

Section: Introductionmentioning

confidence: 99%

Linker-Based Pharmacophoric Design and Semisynthesis of Labdane Conjugates Active against Multi-Faceted Inflammatory Targets

Mohan,

Krishnan,

Madhusoodanan

et al. 2024

J. Agric. Food Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

Indole/isatin‐containing hybrids as potential antibacterial agents

Song

Bian

et al. 2020

Archiv der Pharmazie

View full text Add to dashboard Cite

The emergence and worldwide spread of drug-resistant bacteria have already posed a serious threat to human life, creating the urgent need to develop potent and novel antibacterial drug candidates with high efficacy. Indole and isatin (indole-2,3-dione) present a wide structural and mechanistic diversity, so their derivatives possess various pharmacological properties and occupy a salient place in the development of new drugs. Indole/isatin-containing hybrids, which demonstrate a promising activity against a panel of clinically important Gram-positive and Gram-negative bacteria, are privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, focuses on the development and structure-activity relationship (SAR) of indole/isatincontaining hybrids with potential application for fighting bacterial infections, to facilitate further rational design of novel drug candidates.

show abstract

Cascade Synthesis of New Indole‐Containing Pentacyclic Scaffolds Mediated by Aryl and Iminyl Radicals

Abonia,

García,

Hurtado

et al. 2024

Chemistry An Asian Journal

View full text Add to dashboard Cite

A five‐step approach, starting from simple 1,5‐disubstituted indoles, has been implemented for the synthesis of diversely substituted indole‐pyrido‐indene pentacyclic compounds up to 54% yield via domino radical‐mediated processes in the presence of the radical reagents DLP/TTMSS and AIBN/TTMSS. Reactions proceeded with diverse key starting radical cyano‐precursors strategically synthesized which were subsequently transformed into the target pentacyclic compounds through an aryl/iminyl radical‐mediated domino reactions sequence. In addition to the routine spectroscopic techniques, the structure of radical precursors, as well as, the target pentacyclic products were unequivocally established by single crystal X‐ray diffraction, confirming the effectiveness of the proposed synthetic sequence.

show abstract

Antibacterial and antitubercular evaluation of dihydronaphthalenone‐indole hybrid analogs

Cited by 32 publications

References 30 publications

Linker-Based Pharmacophoric Design and Semisynthesis of Labdane Conjugates Active against Multi-Faceted Inflammatory Targets

Linker-Based Pharmacophoric Design and Semisynthesis of Labdane Conjugates Active against Multi-Faceted Inflammatory Targets

Indole/isatin‐containing hybrids as potential antibacterial agents

Cascade Synthesis of New Indole‐Containing Pentacyclic Scaffolds Mediated by Aryl and Iminyl Radicals

Contact Info

Product

Resources

About