INDEX nitric oxide effects

As 1,2,5-thiadiazole analogues, potent HlV-1 reverse transcriptase inhibitors, some simple 1,2,5-oxadiazoles, compounds 4-6 (Fig. 9), have been synthesized using the traditional Wieland procedure as key for the heterocycle formation [121]. Such as thiadiazole parent compounds, derivative with chlorine atoms on the phenyl ring, i.e., 5, showed the best anti-viral activity. Selectivity index (ratio of cytotoxic concentration to effective concentration) ranked in the order of 5 > 6 > 4. The activity of Fz derivative 6 proved the N-oxide lack of relevance in the studied bioactivity. These products have been claimed in an invention patent [122]. On the other hand, compound 7 (Fig. 9) was evaluated for its nitric oxide (NO)-releasing property (see below) as modulator of the catalytic activity of HlV-1 reverse transcriptase. It was found that NO inhibited dose-dependently the enzyme activity, which is hkely due to oxidation of Cys residues [123]. 

FIGURE 7 Percentage changes in hemodynamic variables from baseline values during a 15-rain administration of inhaled nitric oxide in postoperative neonates with no residual anatomic obstruction to pulmonary blood flow. There was a marked pulmonary vasodilating effect. HR, Heart rate Cl, cardiac index BP, systemic artery pressure SVR, systemic vascular resistance PAP, mean pulmonary artery pressure PVR, pulmonary vascular resistance. 

FIGURE 9 The effects of 80-ppm nitric oxide (NO) inhalation in six patients with transient graft dysfunction after lung transplantation. Pulmonary artery pressure (PAp), pulmonary vascular resistance index (PVRI), and intrapulmonary shunt fraction (Qs/Qt) decreased significantly, while arterial oxygen pressure (PaOi increased. [Adapted and reproduced with permission from Adatia et al. (77).]... 

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