Vadodara: The probability of new anti-TB medicines that would minimize the commonly observed side effects on kidney and liver has brightened with the discovery of new compounds by the researchers of the MS University . The researchers from the Faculty of Pharmacy screened at least two lakh compounds to identify these novel anti-TB agents, which basically inhibit the action of an enzyme responsible for the drug's reaction that damages other organs. The researchers got a patent from the government of India, and their scientific paper has been published in the prestigious UK-based Journal of Biomolecular Structure and Dynamics.
“We virtually screened the compounds using the developed pharmacophore model and other filters like the latest molecular modelling techniques to identify these novel anti-TB agents,” said Dr Prashant R Murumkar from the Faculty of Pharmacy, who, along with his PhD student Dr Monica Chauhan, has been granted the patent. The patent was granted for their discovery of the potent anti-tubercular agents. Currently, TB is treated with a mix of antibiotics that are used to kill the bacteria that cause the disease.
“For most cases, the standard drugs are isoniazid, rifampin, ethambutol, and pyrazinamide. If the bacteria resist these drugs, other options like fluoroquinolones, aminoglycosides, bedaquiline, and delamanid are also used. Using a combination of these drugs helps to treat TB effectively and prevent the bacteria from becoming resistant,” said Murumkar.
“However, the currently used drugs can result in hepatotoxicity (drug-induced liver injury) and nephrotoxicity (the process that occurs when kidneys are damaged by a drug, chemical or toxin resulting in chronic kidney disease). They can cause other side effects to the human body,” said Murumkar. However, the research team at MSU adopted a novel method for TB research.
“Our target was an enzyme which is exclusively present in mycobacteria. The newly designed compounds have the potential to block this enzyme. They can break the cell wall synthesis of the bacteria by inhibiting the DprE1 enzyme,” he said.
This ultimately results in the death of the bacteria. “Since DprE1 is exclusively present in mycobacterium and not in the human being, the side effects in the human body, especially on the kidney and the liver, decrease,” he said. The researchers say the newly developed molecules are the first of their kind, representing pyrazolo-pyrimidine containing scaffold having DprE1 inhibitory anti-TB activity.
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