It said the six companies, including a dairy and day care center, and individuals were involved in the operations of Ismael Zambada Garcia, identified as "one of Mexico's most powerful drug kingpins," who is based in the northwestern state of Sinaloa, home to many of Mexico's top drug smugglers.
"The Zambada Garcia organization cannot hide behind front companies like the Sinaloa cattle and dairy business," Drug Enforcement Administration Administrator Karen P. Tandy said in the news release.
She said her agency was working with the Treasury Department "to expose these traffickers' front companies for what they really are: not legitimate businesses, but illegal cash cows that fuel the drug trade, its violence and corruption."
The department's designation under the so-called Kingpin Act freezes any assets they may have in the U.S. and prohibits anyone in the United States from doing business with them.
The law is meant to expose the networks traffickers use to hide and launder drug money and "cuts them off from the U.S. financial system," according to the Treasury Department statement.
The director of one of the institutions listed, the Nino Feliz day care center in Culiacan, said her operation was "in no way" related to Zambada.
Carmen Olivia, interviewed by telephone, said the center, serving 240 children of working mothers, was privately owned but was financed by the federal Social Security service. "You can't call it a big business. It's more of a humanitarian thing," she said.
She noted that the school is in a rented building and speculated that the ownership of the building might have alarmed U.S. officials, but she said she could not identify the landlord.
Olivia said she feared the listing could affect the school: "What are the mothers going to think?"
A man who answered the phone at Nueva Industria de Ganaderos de Culiacan, a cattle and dairy company in Culiacan, said no one was available to comment.
Mexico's federal Attorney General's Office had no immediate on comment on the announcement.
Among the individuals the Treasury Department identified as fronts were Zambada's former wife, Rosario Niebla Cardoza, and their four daughters.
The State Department has offered a $5 million reward for information leading to Zambada's arrest.