Synthesis of new chiral 1,3,4-thiadiazole-based di- and tri-arylsulfonamide residues and evaluation of in vitro anti-HIV activity and cytotoxicity.

A series of new chiral 1,3,4-thiadiazole-based bis-sulfonamides 4a-4w and tri-sulfonamide analogue 5 was synthesized and evaluated as anti-HIV agents. The reaction of chiral amino acids 1 with sulfonyl chlorides 2, followed by subsequent reaction of resultant N-protected amino acids 2a-2f with thiosemicarbazide in the presence of excess phosphorous oxychloride afforded N-(1-(5-amino-1,3,4-thiadiazol-2-yl)alkyl)-4-arylsulfonamides 3a-3f. Treatment of 2a-2f with substituted sulfonyl chlorides in portions furnished the target bis-sulfonamide analogues 4a-4w in good yields, together with the unexpected 5. The new compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compounds 4s were the most active in inhibiting HIV-1 with IC50 = 9.5 µM (SI = 6.6), suggesting to be a new lead in the development of an antiviral agent. Interestingly, compound 5 exhibited significant cytotoxicity of > 4.09 µM and could be a promising antiproliferative agent.

Microbial biochemical pathways of arsenic biotransformation and their application for bioremediation.

Arsenic is a ubiquitous toxic metalloid, the concentration of which is beyond WHO safe drinking water standards in many areas of the world, owing to many natural and anthropogenic activities. Long-term exposure to arsenic proves lethal for plants, humans, animals, and even microbial communities in the environment. Various sustainable strategies have been developed to mitigate the harmful effects of arsenic which include several chemical and physical methods, however, bioremediation has proved to be an eco-friendly and inexpensive technique with promising results. Many microbes and plant species are known for arsenic biotransformation and detoxification. Arsenic bioremediation involves different pathways such as uptake, accumulation, reduction, oxidation, methylation, and demethylation. Each of these pathways has a certain set of genes and proteins to carry out the mechanism of arsenic biotransformation. Based on these mechanisms, various studies have been conducted for arsenic detoxification and removal. Genes specific for these pathways have also been cloned in several microorganisms to enhance arsenic bioremediation. This review discusses different biochemical pathways and the associated genes which play important roles in arsenic redox reactions, resistance, methylation/demethylation, and accumulation. Based on these mechanisms, new methods can be developed for effective arsenic bioremediation.

Redox biotransformation of arsenic along with plant growth promotion by multi-metal resistance Pseudomonas sp. MX6.

Remediation of toxic metal-polluted sites by microorganisms is an environment-friendly remediation technique. Multi-metal-resistant bacteria were isolated from a wastewater treatment plant showing resistance against As(III), As(V), Cr, Co, Cu, Cd, Hg, Ni, Pb, Se and Zn. Maximum resistance against all metals was shown by the bacterial isolate MX-6 (As 20mM, Cd 30mM, Cr 5.0mM, Co 25mM, Cu 25mM, Ni 20mM, Zn 30mM, Pb 15mM, Se 20mM and Hg 2.5mM), which was identified as Pseudomonas sp. through 16S rDNA sequencing. Pseudomonas sp. MX-6 reduced 506µM As(V) and also oxidized 160µM As(III). The genes for As, Cd, Se and Zn resistance in Pseudomonas sp. MX-6 were found to be plasmid borne, as indicated by transformation. Pseudomonas sp. MX-6 produced 49.37µg·mL-1 IAA and was also positive for HCN production and phosphate solubilisation. The bacterial isolate also supported Vigna radiata growth, both in the absence and presence of the aforementioned metals. Such bacteria can be used as biofertilizers to reclaim the polluted lands and to enhance crop production in metal-contaminated soils.