Research Projects

Rationale of the research: The emergence and spread of drug-resistant human pathogenic fungi that have acquired different drug resistance mechanisms continue to threaten the ability to treat common fungal infections. The current antifungal strategy needs to be improved given the limitations and accessibility of antifungal treatment regimens at the moment. Moreover, the currently available antifungal drug classes are becoming increasingly ineffective against different fungal pathogens, besides the poor efficacy and their unfavorable side effects all indicating the urgent requirement for the establishment of novel therapeutic approaches. Given the aforementioned scenario, the current suggested work focussed on developing modified azole antifungals offers a lot of potential for implementation and global medical industry expansion. The study involves looking for alternative drugs and treatments in an effort to broaden the selection of antifungal defence strategies. Crystal engineering represents a modern strategy for creating molecules with the required characteristics in this context. The synthesized molecule/co-crystal (modified azole antifungals) will be an ideal alternative means of standard drug intake enhancing the overall bioavailability of the parent drug by increasing solubility without compromising the drug activity. Scientific objectives: The study has been framed to involve the following objectives: Synthesis and physiochemical studies of pharmaceutical co-crystals of azole antifungals; Detailed analysis of antifungal properties of pharmaceutical co-crystals of azole antifungals and Evaluation of cytotoxicity and in-vivo antifungal activity potential of pharmaceutical co-crystals of azole antifungals. Hypothesis/model to be tested: These modified azole antifungals will display a very high potential to be evolved into antifungals with potent antifungal activity, minimal cytotoxicity and higher bioavailability since they are anticipated to demonstrate superior action at low effective drug concentrations. Main experiments : Synthesis/physiochemical studies related experiments; Antifungal properties analysis related experiments (MIC and other drug susceptibility assays); Cytotoxicity (MTT and LDH assays)/in-vivo antifungal activity related experiments. Significance:The proposed study highlighting the synthesized azole cocrystals, with the mechanism of action comparable to standard azoles, can be preferred as an alternative to the parent azole drugs against different human pathogenic fungi since the cocrystals can have better bioavailability (leading to increased antifungal activity at less effective drug concentration) owing to its increased solubility and subsequently are expected to show less host toxicity.