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

Figures & data

Figure 1. Synthesis scheme of MCD-KV-10. Synthesis of compound A: phenylisothiocyanate reacts with acetamidine to form of an adduct which further reacts with dichloroacetone to form compound A. Synthesis of compound B: methylacetoacetate reacts with ammonia to form enamine which on subsequent reaction with phenylisothiocyanate forms compound B. Synthesis of MCD-KV-10: Compound A reacts with compound B in the presence of dimethylformamide at room temperature for 4 h to produce MCD-KV-10.

Table 1. K_i values from radioligand binding experiment for MCD-KV-10 at A₁, A_2A and A₃ receptor subtypes.

	Adenosine receptor subtypes
Compound	A1	A2A	A3
MCD-KV-10	9680 (6190–15 100)	4820 (3770–6180)	797 (564–1130)

Values are K_i values and are given in nM with 95% confidence intervals in parentheses.

Figure 2. Mast cell degranulation in intestinal mesenteric tissues of guinea pigs. Data expressed as mean ± SD (n = 6).

Figure 3. Intact and degranulated mast cells in the intestinal mesenteric tissues of (a) disease control, (b) positive control and (c) test group (MCD-KV-10) animals.

Figure 4. Respiratory rate in guinea pigs of all groups before and after acetylcholine (ACh) challenge. Data expressed as mean ± SD (n = 6). *p ≤ 0.05 as compared to disease control group.

Figure 5. Tidal volume in guinea pigs of all groups before and after acetylcholine (ACh) challenge. Data expressed as mean ± SD (n = 6). *p ≤ 0.05 as compared to disease control group.

Table 2. Total WBC count in blood and BAL fluid of guinea pigs.

	WBC in blood (×10^−3/µL)		WBC in BAL fluid (×10^−3/µL)
Groups	Day 17	Day 22	Day 22
Normal control	8.03 ± 0.35	8.525 ± 0.48	7.48 ± 1.17
Disease control*	9.45 ± 0.31	15.475 ± 2.01	19.08 ± 1.82
Positive control	9.40 ± 0.84	7.95 ± 1.98	7.25 ± 0.97
MCD-KV-10	11.73 ± 0.80	8.825 ± 1.54	8.45 ± 1.02

Data expressed as mean ± SD, (n = 6).

*p ≤ 0.05 as compared to disease control group.

Table 3. Differential count in BAL fluid of guinea pigs.

Groups	Lymphocytes	Neutrophils	Mixed
Normal control	61.08 ± 1.86	36.58 ± 2.65	2.34 ± 0.39
Disease control*	34.75 ± 4.68	53.68 ± 4.89	11.57 ± 1.51
Positive control	59.76 ± 2.38	32.28 ± 2.17	7.96 ± 1.29
Test group (MCD-KV-10)	54.55 ± 3.57	38.23 ± 2.57	7.22 ± 1.11

Data expressed as mean ± SD, (n = 6).

*p ≤ 0.05 as compared to disease control group.

Figure 6. Effect of treatments on serum cytokine levels of guinea pigs. Data expressed as mean ± SD, (n = 6). *p ≤ 0.05 as compared to disease control group.

Figure 7. Effect of treatments on BAL fluid cytokine levels of guinea pigs. Data expressed as mean ± SD, (n = 6). *p ≤ 0.05 as compared to disease control group.

Figure 8. Effect of treatments on lung histamine levels of guinea pigs. Data expressed as mean ± SD, (n = 6). *p ≤ 0.05 as compared to disease control group.

Figure 9. Histomicrographs of lung tissue of (a) normal control, (b) disease control, (c) positive control and (d) test group (MCD-KV-10) animals.