Legendary Mexican footballer Rafael Marquez Alvarez and a well-known band leader are among 22 people sanctioned for alleged ties to a drug-trafficking organisation, the US Treasury Department announced on Wednesday.

The sanctions are the result of a multi-year investigation of the drug-trafficking organisation allegedly headed by Raul Flores Hernandez, the department said in a statement.

It will also sanction 43 entities in Mexico, including a football team and casino.

It is the single largest such designation of a drug-trafficking organisation ever by its Office of Foreign Assets Control, the statement said.

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Marquez, 38, is a former defender for Barcelona, Monaco and New York Red Bulls who currently plays for the Mexican soccer club Atlas in Guadalajara and is captain of the Mexican national team.

Marquez denied having any links to drug traffickers.

"I categorically deny any kind of relation to this organisation," Marquez said in a statement on Wednesday, adding: "Today is my most difficult match; I will try to clear all of this up."

The sanctions freeze all US assets of the people and entities named and forbid US citizens from doing business with them.

Raul Flores Hernandez: 'E xtraordinarily crafty'

Flores Hernandez allegedly operated independently in the northern city of Guadalajara but maintained alliances with the Sinaloa and Jalisco New Generation cartels. The attorney general's office said Flores Hernandez was arrested on July 20 and is being held while his extradition is pending.

The Mexican Attorney General's Office also seized related assets on Wednesday, including the Grand Casino near Guadalajara, according to the US statement.

Mexican prosecutors said they were working closely with US authorities on the investigation and added that Marquez came voluntarily to the Attorney General's Office to provide a statement.

Mike Vigil, former chief of international operations for the US Drug Enforcement Administration and author of the book Deal, said 64-year old Flores Hernandez has been in the business since the 1980s.

"He is extraordinarily crafty in the way he strategises and the way that he navigates between cartels," Vigil told the Associated Press news agency.

But, the former agent added, Flores Hernandez has remained a mid-level drug trafficker, never forming what one would call a cartel, and of late had aligned himself with Nemesio Oseguera of the Jalisco New Generation Cartel.

Vigil said Flores Hernandez had a real talent for laundering drug proceeds by setting up front companies. He said it would be difficult to imagine that Marquez didn't know who he was dealing with because Flores Hernandez has been around for so long.

"Raul Flores Hernandez has operated for decades because of his long-standing relationships with other drug cartels and his use of financial front persons to mask his investments of illegal drug proceeds," John E Smith, director of the Office of Foreign Assets Control, said in the statement.

Federal drug trafficking indictments against Flores Hernandez were returned in March in Washington and the southern district of California.

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The US government referred to Marquez and 34-year-old norteno singer Julio Cesar Alvarez, better known as Julion Alvarez, as people with long-standing relationships with Flores Hernandez who "have acted as front persons for him and his [drug-trafficking organisation] and held assets on their behalf".

Alvarez has been nominated for Latin Grammys and has won Billboard awards.

Alvarez posted a video to his Facebook page saying "absolutely nothing is going on". Alvarez called Marquez a friend and sent him a hug: "Everything they are saying there can be cleared up."

The US statement did not say that Marquez or Alvarez face charges in the US.

A Mexican all-time great

Marquez is famed as a tenacious defender whose crunching tackles have sometimes seen him sent off in high-profile matches. In Mexico he is revered as one of the country's all-time greats.

Marquez debuted in Mexico's top-flight league in 1996 with Atlas and moved to AS Monaco of France's Ligue 1 three years later. In 2003, Marquez joined Barcelona and spent 10 years there, helping the Catalan super-club win Spanish league and Champions League trophies.

Advancing into his 30s, Marquez then had stints with the New York Red Bulls of Major League Soccer, Leon of Mexico and Hellas Verona in Italy's Serie A before returning to Atlas.

A longtime fixture of Mexico's national team, he led "El Tri" at four World Cups and has hoped to become only the third player ever to compete in five. Marquez has scored 13 goals wearing the green jersey in 158 appearances between 1997 and 2017, according to statistics published by the Mexican Soccer Federation.

Speaking in a briefing to reporters, a high-level Treasury Department official said the association between Marquez and Flores Hernandez went back at least 20 years and Marquez served as "an important" frontman for money laundering.

Under the terms of the briefing, the official could not be named. Among the entities that the department cited were his football academy and health and rehabilitation clinics.

Vigil said cartel figures have long been drawn to football stars and musicians.

"They love soccer ... so they love to associate with sports figures," Vigil said. "Who else do they like? They like these norteno singers, because these guys create ballads about their exploits and it adds to their legend, to the folklore."