Implication of novel thiazolo-thiophene derivative (MCD-KV-10) for management of asthma

Abstract

Context: Asthma is multifaceted disease where many targets contribute towards its development and progression. Among these, adenosine receptor subtypes play a major role. Objective: MCD-KV-10, a novel thiazolo-thiophene was designed and evaluated pre-clinically for its implication in management of asthma. Materials and methods: This compound showed good affinity and selectivity towards A 2A /A 3 adenosine receptor (AR) subtypes. Furthermore, MCD-KV-10 was evaluated for in vitro lipoxygenase inhibition activity; in vivo mast cell stabilization potential and in vivo anti-asthmatic activity was done in ovalbumin-induced airway inflammation model in guinea pigs. Results: The compound showed good (457%) inhibition of lipoxygenase enzyme and also effectively protected mast cell degranulation (463%). The compound showed good anti-asthmatic activity as inferred from the in vivo studies. Discussion: These results indicate that MCD-KV-10 has an inhibitory effect on airway inflammation. Conclusion: Though, we have identified a potential candidate for management of asthma, further mechanistic studies are needed.

Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

“…In in vitro assays, when using compound 4 at a concentration of 100 µg/mL, inhibition of the enzyme 5-LOX was observed at approximately 57%. As with other thiophene derivatives with anti-inflammatory activity, compound 4 presents methyl, ester, and amine groups in its structure [ 45 ].…”

“…Patil et al [ 45 ] evaluated new thiazolo-thiophene derivatives in an asthma model, and found that compound 4 ( Figure 2 ) was able to significantly reduce the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) observed in bronchoalveolar lavage.…”

α-Terthienylmethanol, isolated from Eclipta prostrata, induces apoptosis by generating reactive oxygen species via NADPH oxidase in human endometrial cancer cells

“…Thiophenes have various biological activities, including anti-microbial (Nasr et al, 2014), anti-asthma (Patil et al, 2014), anti-rheumatic (Sherif and Hosny, 2014), anti-inflammatory (Bailey et al, 1988), and anti-cancer activities (Ghorab et al, 2014;Said and Elshihawy, 2014); (Yang et al, 2014). Naturally occurring polythiophenes such as terthiophenes, in which thiophenes are attached through α-positions next to the sulfur atoms, are commonly found in plants of the family Asteraceae (Compositae) (Hudson et al, 1994) and have been proven to possess several biological activities (Ciofalo and Table 2 Cytotoxic analysis of the various compounds from the n-hexane fraction and cisplatin.…”

Development of Thiophene Compounds as Potent Chemotherapies for the Treatment of Cutaneous Leishmaniasis Caused by Leishmania major

“…There is an urgent need for new therapeutics that are more effective and less toxic than conventional treatments used to treat infectious diseases, including leishmaniasis [ 25 ]. Thiophenes derivatives are known for their therapeutic applications and have shown promising results to treat different types of cancer, degenerative diseases, HIV, and malaria [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Thus, we evaluated the anti-leishmania activity and selectivity of nine thiophene derivatives against L. major , and potential MOA was elucidated for our best candidate, 5D .…”