Dual Antitubercular and Antileishmanial Profiles of Quinoxaline Di-N-Oxides Containing an Amino Acidic Side Chain.

We present a new category of quinoxaline di-N-oxides (QdNOs) containing amino acid side chains with dual antituberculosis and antileishmanial activity. These compounds were synthesized by combining a regioselective 2,5-piperazinedione opening and a Beirut reaction and were screened for their activity against Mycobacterium tuberculosis and the promastigote and amastigote forms of representative species of the Leishmania genus. Most QdNOs exhibited promising antitubercular activity with IC50 values ranging from 4.28 to 49.95 µM, comparable to clinically established drugs. Structure-activity relationship analysis emphasized the importance of substituents on the aromatic ring and the side chain. Antileishmanial tests showed that some selected compounds exhibited activity comparable to the positive control miltefosine against promastigotes of Leishmania amazonensis and Leishmania donovani. Notably, some compounds were found to be also more potent and less toxic than miltefosine in intracellular amastigote assays against Leishmania amazonensis. The compound showing the best dual antitubercular and leishmanicidal profile and a good selectivity index, 4h, can be regarded as a hit compound that opens up new opportunities for the development of integrated therapies against co-infections.

Profile of intestinal parasitic infections in human immunodeficiency virus/acquired immunodeficiency syndrome patients in Northeast India.

INTRODUCTION: Diarrhea is one of the major complications occurring in over 90% of human immunodeficiency virus (HIV)-infected individuals in developing countries. Coccidian group of parasitic infections remain the standout opportunistic pathogens in many parts of the world. AIM: The objective was to understand the profile of diarrheagenic parasites in HIV/AIDS patients along with analysis of the changing trends in the profile of parasitic diarrhea with special context to coccidian parasitic infections. METHODOLOGY: A cross-sectional study was performed at "ID CENTRE FOR NORTHEAST," Shillong, from January 2014 to October 2017. Stool samples collected were observed microscopically for parasites both on direct and concentrated stool samples under ×10 and ×40 magnification. Modified acid-fast staining was used for the detection of coccidian parasites. All statistical analyses were performed using IBM SPSS software, Version 24.0. RESULTS: The prevalence of intestinal parasitic infections was 40.99%, coccidian parasitic infection accounted for 85.13% of total intestinal parasitic infections. Cryptosporidium parvum was the most common cause of diarrhea (70.64%), followed by Cystoisospora belli (23.81%) and Cyclospora spp. (5.55%). Trend analysis of coccidian etiology during the study revealed a significant rise in the positivity of Cryptosporidium spp. and a decrease in the Cystoisosporiasis belli infection. The common noncoccidian parasites identified include hookworm (8.1%) followed by Ascaris lumbricoides (4.7%). CONCLUSION: The magnitude of parasitic infections is considerably high among the HIV/AIDS patients in Northeast India, and it is essential for screening and periodic monitoring of all the HIV patients for coccidian parasites by stool microscopy.