Antitubercular effect of 8-[(4-Chloro phenyl) sulfonyl]-7-Hydroxy-4-Methyl-2H-chromen-2-One in guinea pigs

Abstract

Objective: TO EVALUATE THE ANTITUBERCULAR EFFICACY AND SAFETY OF NEW CHEMICAL ENTITY (NCE): 8-[(4-Chloro phenyl) sulfonyl]-7-Hydroxy-4-Methyl-2H-chromen-2-One (CSHMC) in guinea pigs.

Materials and methods: This pilot study was carried out in guinea pigs. They were infected with M. tuberculosis H(37)Rv (1.5 × 10(4) cfu/guinea pig) via intramuscular route. After 30 days, infections were confirmed in 6 guinea pigs by histopathology of spleen, lung, and liver. After that CSHMC (5 and 20 mg/kg) was administered for 1 month and its effect was compared with vehicle, rifampicin (60 mg/kg) and isoniazid (30 mg/kg). Efficacy of CSHMC was evaluated on the basis of histopathologic scoring of lesion in lung, spleen, liver, and safety on the basis of measuring hemogram, liver and renal function parameters.

Results: Isoniazid, rifampicin, and CSHMC (20 mg/kg) significantly reduce the median lesion score in lung, spleen, and liver as compared to disease control group. Reduction in median lesion score for lung and spleen were not statistically significant for CSHMC 5 mg/kg. CSHMC (20 and 5 mg/kg) did not produce any changes in hemogram, liver and renal function parameters with respect to normal values.

Conclusions: CSHMC had shown significant antitubercular efficacy comparable to isoniazid and rifampicin and did not show hematological, hepato- and nephrotoxicity.

Keywords: Isoniazid; rifampicin; tuberculosis.

Figure 1

Chemical structure of (a) coumarin; (b) dapsone (diaminodiphenyl sulfone [DADS]); (c) 8-[(4-Chloro phenyl) sulfonyl]-7-hydroxy-4-methyl-2H-chromen-2-One

Figure 2

Histopathology of lung (H and E stain, ×40). (a) Normal control group—normal alveolar morphology; (b) disease control group—severe (score 6) epithelioid cells (E), lymphocyte (L), alveolar wall infi ltration (A), caseation necrosis (CN), and giant cells (G); (c–e) isoniazid, rifampicin, and CSHMC (20 mg/kg) treated group—minimal (score 0.5–1) epithelioid cells and alveolar wall infi ltration with no caseation necrosis and giant cell; (f) CSHMC (5 mg/kg) treated group—mild (score 1.5) epithelioid cells and alveolar wall infi ltration with no caseation necrosis and giant cell

Figure 3

Histopathology of spleen (H and E stain, ×40). (a) Normal control group—normal morphology; (b) disease control group—severe (score 6) epithelioid cells (E), lymphocyte (L) infi ltrate with caseation necrosis (CN), and giant cells (G); (c–e) isoniazid, rifampicin, and CSHMC (20 mg/kg) treated group—minimal to mild (score 1–1.5) epithelioid cells infi ltration with no caseation necrosis and giant cell; (f) CSHMC (5 mg/kg) treated group—mild to moderate (score 2.5) epithelioid cells infi ltration with no caseation necrosis and giant cell

Figure 4

Histopathology of liver (H and E stain, ×40). (a) Normal control group—liver shows normal morphology; (b) disease control group—a mild (score 2) ballooning degeneration (BD); (c–f) isoniazid, rifampicin, and CSHMC (20 and 5 mg/kg) treated group—a minimal or no (score 0.5) ballooning degeneration (BD)