The mutually exclusive cross-resistance patterns of these mutants provide a highly specific means to distinguish the two kinds of podophyllotoxin derivatives. Mutant Chinese hamster cells resistant to podophyllotoxin are affected in a protein P1 that was later identified as the mammalian HSP60 or chaperonin protein.Furthermore, podophyllotoxin is classified as an arytetralin lignan for its ability to bind and deactivate DNA. It and its derivates bind Topo II and prevent its ability to catalyze rejoining of DNA that has been broken for replication. Lastly, experimental evidence has shown that these arytetralin lignans can interact with cellular factors to create chemical DNA adducts, thus further deactivating DNA. Chemistry
Structural characteristic
The structure of podophyllotoxin was first elucidated in the 1930s. Podophyllotoxin bears four consecutive chiral centers, labelled C-1 through C-4 in the following image. The molecule also contains four almost planar fused rings. The podophyllotoxin molecule includes a number of oxygen containing functional groups: an alcohol, a lactone, three methoxy groups, and an acetal. Derivatives of podophyllotoxin are synthesized as properties of the rings and carbon 1 through 4 are diversified. For example, ring A is not essential to antimitotic activity. Aromatization of ring C leads to loss of activity, possibly from ring E no longer being placed on the axial position. In addition, the stereochemistry at C-2 and C-3 configures a trans-lactone, which has more activity than the cis counterpart.
Wearing of broad protective glasses with side shields is recommended for people at risk for such injuries. Treatment
A presumptive diagnosis of fungal keratitis requires immediate empirical therapy. Natamycin ophthalmic suspension is the drug of choice for filamentous fungal infection. Fluconazole ophthalmic solution is recommended for Candida infection of the cornea. Amphotericin B eye drops may be required for non-responding cases, but can be quite toxic and requires expert pharmacist for preparation. Other medications have also been tried with moderate success. An updated Cochrane Review published in 2015 looking at the best treatment for fungal keratitis could not draw any conclusions as the studies included used different medications. The review did find that "people receiving natamycin were less likely to  develop a hole in their cornea and need a transplant." Prognosis
The infection typically takes a long time to heal, since the fungus itself is slow growing. Corneal perforation can occur in patients with untreated or partially treated infectious keratitis and requires surgical intervention in the form of corneal transplantation. Epidemiology
This disease is quite common in the tropics and with large agrarian population. India has a high number of cases with fungal keratitis, but poor reporting system prevents accurate data collection. Florida in US regularly reports cases of fungal keratitis, with Aspergillus and Fusarium spp. as the most common causes. According to the Global Action Fund for Fungal Infections, every year there are around 1 million cases of blindness due to fungal keratitis.