Antimosquito properties of 2-substituted phenyl/benzylamino-6-(4-chlorophenyl)-5-methoxycarbonyl-4-methyl-3,6-dihydropyrimidin--ium chlorides against Anopheles arabiensis.

Eight novel dihydropyrimidine analogs named DHPM1-DHPM8 was synthesized in their hydrochloride salt form using one pot synthesis between methyl 2-chloro-4-(4-chlorophenyl)-6-methyl-1,4-dihydropyrimidine-5-carboxylate and substituted arylamines in isopropanol. The antimosquito effect of the test compounds were assessed against the adult mosquito Anopheles arabiensis. For adulticidal properties the test compounds were sprayed onto ceramic tiles and screened using the cone bio-assay method. The larvicidal activity was tested by monitoring larval mortality daily and up to 3 days of exposure. Repellency properties were tested in a feeding-probe assay using unfed female Anopheles arabiensis. Compounds DHPM1, DHPM4, DHPM5 and DHPM6 exerted larval mortality equivalent to temephos (trade name Abate, a commercial larvicidal compound). Compounds DHPM1 to DHPM5 repelled or knocked down 92 to 98% of mosquitoes exposed to rodent skin treated with the compounds. None of the compounds showed any significant activity against the adult mosquito Anopheles arabiensis.

Evaluation of halogenated coumarins for antimosquito properties.

Mosquitoes are the major vectors of parasites and pathogens affecting humans and domestic animals. The widespread development of insecticide resistance and negative environmental effects of most synthetic compounds support an interest in finding and developing alternative products against mosquitoes. Natural coumarins and synthetic coumarin analogues are known for their several pharmacological properties, including being insecticidal. In the present study halogenated coumarins (3-mono/dibromo acetyl, 6-halogenated coumarin analogues) were screened for larvicidal, adulticidal, and repellent properties against Anopheles arabiensis, a zoophilic mosquito that is one of the dominant vectors of malaria in Africa. Five compounds exerted 100% larval mortality within 24 h of exposure. All coumarins and halogenated coumarins reversibly knocked down adult mosquitoes but did not kill them after 24 h of exposure. Repellent properties could not be evidenced. Five compounds were considered potential larvicidal agents for further research and development, while adulticidal activity was considered only mild to moderate.

Synthesis and antitubercular activity of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides.

A series of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides 7-13 and 15 was synthesized in their hydrochloride salt form. The title compounds were characterized by FT-IR, NMR ((1)H and (13)C) and elemental analysis. They were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, multidrug resistance tuberculosis and extensively drug resistance tuberculosis by agar diffusion method and tested for the cytotoxic action on peripheral blood mononuclear cells by MTT assay. Among all the tested compounds in the series, compounds 7 and 11 emerged as promising antitubercular agents at 16 µg/mL against multidrug resistance tuberculosis and over 64 µg/mL against extensively drug resistance tuberculosis. The conformational features and supramolecular assembly of the promising compounds 7 and 11 were determined by single crystal X-ray study.

Total synthesis of a depsidomycin analogue by convergent solid-phase peptide synthesis and macrolactonization strategy for antitubercular activity.

Depsidomycin is a cyclic heptadepsi-peptide isolated from the cultured broth of Streptomyces lavendofoliae MI951-62F2. It exhibits significant antimicrobial and immunosuppressive activity. The total synthesis of a depsidomycin analogue in which 1,2-piperazine-3-carboxylic acid was substituted with proline is described. After several trials using different strategies, the desired depsidomycin analogue was obtained via stepwise synthesis starting by the amino acid 'head' and macrolactonization under Yamaguchi conditions. The cyclic depsipeptide was evaluated to have an minimum inhibitory concentration (MIC) of 4 µg/ml against H37RV and 16 µg/ml against MDR clinical strains of MTB (MDR-MTB), while the linear precursor 8 also had MICs of 4 and 16 µg/ml for the susceptible and resistant strains, respectively.