Synthesis, antiamoebic activity and docking studies of metronidazole-triazole-styryl hybrids.

A series of 22 novel metronidazole-triazole-styryl hybrids were synthesized and evaluated for their in vitro antiamoebic activity against HM1: IMSS strain of Entamoeba histolytica. Some of the hybrids were found to be more active (IC50 = 0.12-0.35 µM) than the reference drug metronidazole (IC50 = 1.79 µM). The most active compounds were found to be non-toxic (up to 50 µM) against the Vero cells showing a good safety profile of these hybrids. The docking and ADMET studies were also conducted to investigate the probable mode of action. Docking studies showed significant binding affinity in the active site of E. histolytica thioredoxin reductase (EhTrR) protein.

Marine Peptides as Anticancer Agents: A Remedy to Mankind by Nature.

BACKGROUND: In the search of bioactive molecules, nature has always been an important source and most of the drugs in clinic are either natural products or derived from natural products. The ocean has played significant role as thousands of molecules and their metabolites with different types of biological activity such as antimicrobial, anti-inflammatory, anti-malarial, antioxidant, anti HIV and anticancer activity have been isolated from marine organisms. In particular, marine peptides have attracted much attention due to their high specificity against cancer cell lines that may be attributed to the various unusual amino acid residues and their sequences in the peptide chain. This review aims to identify the various anticancer agents isolated from the marine system and their anticancer potential. METHOD: We did literature search for the anticancer peptides isolated from the different types of microorganism found in the marine system. Total one eighty eight papers were reviewed concisely and most of the important information from these papers were extracted and kept in the present manuscript. RESULTS: This review gives details about the isolation, anticancer potential and mechanism of action of the anticancer peptides of the marine origin. Many of these molecules such as aplidine, dolastatin 10, didemnin B, kahalalide F, elisidepsin (PM02734) are in clinical trials for the treatment of various cancers. CONCLUSION: With the interdisciplinary and collaborative research and technical advancements we can search more promising and affordable anticancer drugs in future.

Anti-methicillin resistant Staphylococcus aureus activity, synergism with oxacillin and molecular docking studies of metronidazole-triazole hybrids.

MRSA causes 60-70% of Staphylococcus aureus infection in hospitals and it has developed resistance against the currently available drugs. Interestingly, a series of 35 metronidazole-triazole hybrids on screening against MRSA were found to be active. Compound 22 was found to be effective at 4 µg/mL concentration against nine strains of MRSA. The inhibitory activity was further enhanced upto 1 µg/mL when this compound was used in combination with oxacillin in 1:1 ratio. All the compounds were found to be non-toxic in THP-1 cell line upto a concentration of 50 µM. The time-kill kinetics studies suggested bacteriostatic nature of the compounds. In silico studies show that these compounds interact with Thr600, Ser598, Asn464, His583 and Tyr446 in the active site of PBP2a crystal structure from MRSA.

The anti-tuberculosis agents under development and the challenges ahead.

Tuberculosis (TB) is a serious health problem causing 1.5 million deaths worldwide. After the discovery of first-line anti-TB drugs, the mortality rate declined sharply, however, the emergence of drug-resistant strains and HIV co-infection have led to increased incidence of this disease. A number of new potential antitubercular drug candidates with novel modes of action have entered clinical trials in recent years. Compounds such as gatifloxacin, moxifloxacin and linezolid, the already known antibiotics are currently being evaluated for their anti-TB activity. OPC-67683 and TMC207 have been approved for the treatment of MDR-TB patients recently, while PA-824, SQ109, PNU-100480, AZD5847, LL3858, SQ609, SQ641, BTZ043, DC-159a, CPZEN-45, Q-203, DNB1, TBA-354 are in various phases of clinical and preclinical developments. This review evaluates the current status of TB drug development and future aspects.

In vitro antiamoebic activity evaluation and docking studies of metronidazole-triazole hybrids.

An in-house database of 520 compounds was docked against Entamoeba histolytica thioredoxin reductase (EhTrR), a promising target for the treatment of amoebiasis. Amongst these, some metronidazole (MTZ)-triazole hybrids were ranked high, with docking scores from -10.23 to -7.56. Studies of the binding orientations and conformations show that the head groups of MTZ-triazole hybrids interact with the arginine residues within the binding pocket of EhTrR, making it clear that such is the optimal and most reliable orientation for this class of compounds. The top-ten MTZ-triazole hybrids were then selected for evaluation of their activity against the HM1:IMSS strain of amoeba. The most active compound, 2-pyridyl-(1,2,3-triazolyl)metronidazole 10, with an IC50 value of 8.4 nM, was significantly more active than the standard drug MTZ alone. Docking studies revealed that compound 10 may act as an EhTrR inhibitor with activity in the nanomolar range and satisfactory ADME properties; it is a suitable candidate to be carried forward as a potential lead in the discovery of drugs to combat amoebiasis.